subject:(Immunomodulation)

1. Zabarsky, Zachary. Immunomodulation as a Potential Therapeutic Strategy Following Spinal Cord Contusion Injury to Limit Tissue Damage and Improve Functional Recovery.

Degree: 2019, Wake Forest University

URL: http://hdl.handle.net/10339/93955

► Spinal cord injuries (SCI) are a debilitating neurological trauma with about 500,000 new cases occuring worldwide every year. Outside of decompression surgery and physical therapy,… (more)

Subjects/Keywords: Immunomodulation

…ABSTRACT Zachary K. Zabarsky IMMUNOMODULATION AS A POTENTIAL THERAPEUTIC STRATEGY FOLLOWING… …for SCI patients. xi CHAPTER I INTRODUCTION IMMUNOMODULATION- A PROMISING TREATMENT… …known as secondary injury. Immunomodulation is a potential treatment strategy to curtail… …along the injury timeline. Immunomodulation and neuroprotection strategies are often studied… …demonstrate potential for immunomodulation as a viable treatment strategy for translational use, as…

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APA (6^th Edition):

Zabarsky, Z. (2019). Immunomodulation as a Potential Therapeutic Strategy Following Spinal Cord Contusion Injury to Limit Tissue Damage and Improve Functional Recovery. (Thesis). Wake Forest University. Retrieved from http://hdl.handle.net/10339/93955

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zabarsky, Zachary. “Immunomodulation as a Potential Therapeutic Strategy Following Spinal Cord Contusion Injury to Limit Tissue Damage and Improve Functional Recovery.” 2019. Thesis, Wake Forest University. Accessed January 23, 2021. http://hdl.handle.net/10339/93955.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zabarsky, Zachary. “Immunomodulation as a Potential Therapeutic Strategy Following Spinal Cord Contusion Injury to Limit Tissue Damage and Improve Functional Recovery.” 2019. Web. 23 Jan 2021.

Vancouver:

Zabarsky Z. Immunomodulation as a Potential Therapeutic Strategy Following Spinal Cord Contusion Injury to Limit Tissue Damage and Improve Functional Recovery. [Internet] [Thesis]. Wake Forest University; 2019. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/10339/93955.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zabarsky Z. Immunomodulation as a Potential Therapeutic Strategy Following Spinal Cord Contusion Injury to Limit Tissue Damage and Improve Functional Recovery. [Thesis]. Wake Forest University; 2019. Available from: http://hdl.handle.net/10339/93955

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Victoria University of Wellington

2. Lambert, Callum. Investigation of Bartonella quintana Host Immune Evasion.

Degree: 2018, Victoria University of Wellington

URL: http://hdl.handle.net/10063/7723

► Bartonella is a genus of gram-negative alphaproteobacteria that infect mammals, causing both acute and chronic disease. Bartonella are re-emerging infectious pathogens that cause a variety… (more)

▼ Bartonella is a genus of gram-negative alphaproteobacteria that infect mammals, causing both acute and chronic disease. Bartonella are re-emerging infectious pathogens that cause a variety of clinical syndromes in humans worldwide, including cat scratch disease, trench fever, bacillary angiomatosis, and endocarditis. Bartonella spp. are spread by biting arthropods such as the sand fly, cat flea, and body louse, and have been isolated from almost all mammalian species tested. Bartonella are a re-emerging concern as the number of confirmed Bartonella diagnoses are increasing, primarily in immunocompromised groups, homeless populations, refugee camps, and in veterinary workers. The three primary human disease-causing Bartonella spp. are B. henselae, B. quintana, and B. bacilliformis. Bartonella are known to subvert the host immune system and persist within the host, often causing bacteraemia which is difficult to effectively diagnose and treat. B. quintana infects humans; after introduction to the skin the bacteria implement numerous immune evasion mechanisms to enter the bloodstream and invade erythrocytes. The mechanisms by which B. quintana modulates and evades the immune system during early infection are almost entirely unknown. Following exposure to B. quintana, the bacteria encounter host immune cells but survive, evading these cells and disseminating into the lymphatic system and eventually bloodstream. This thesis project aimed to dissect the interactions between B. quintana and the human innate immune system to better understand the early stages of infection. A gentamicin protection assay was developed to investigate the ability of THP-1 macrophages, representing human macrophages present in the skin, to internalise B. quintana. These data revealed THP-1 cells were unable to effectively internalise B. quintana, although the mechanism responsible was not determined. Subsequent experiments investigated the role of the B. quintana Type IV secreted effector protein BepA1 in the inhibition of internalisation. Bacterial effector proteins often pathogenically modulate host cell signalling to benefit the bacteria, i.e., altering the actin cytoskeleton to inhibit phagocytosis or supressing immune responses. It was hypothesised BepA1 could play a role in inhibiting phagocytosis; therefore, the host cell target of BepA1 was investigated with a yeast two-hybrid system assay. The human protein Myozap was uncovered as a potential protein that interacts with BepA1. Myozap is expressed in cardiac and lung tissue as well as epithelial and endothelial cells, where it modulates Rho-dependent actin signalling, potentially affecting the actin cytoskeleton and the transcription factor MRTF-A, which influences immune reaction through modulation of NF-κB. To investigate the functional effects of BepA1 activity in host cells, HeLa cells were transfected with BepA1; cell migration and cytokine secretion were assessed, revealing a decrease in pro-inflammatory cytokines in BepA1-transfected cells in response to TNF-a stimulation. These… Advisors/Committee Members: MacKichan, Joanna.

Subjects/Keywords: Bartonella; BepA1; Immunomodulation

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APA (6^th Edition):

Lambert, C. (2018). Investigation of Bartonella quintana Host Immune Evasion. (Masters Thesis). Victoria University of Wellington. Retrieved from http://hdl.handle.net/10063/7723

Chicago Manual of Style (16^th Edition):

Lambert, Callum. “Investigation of Bartonella quintana Host Immune Evasion.” 2018. Masters Thesis, Victoria University of Wellington. Accessed January 23, 2021. http://hdl.handle.net/10063/7723.

MLA Handbook (7^th Edition):

Lambert, Callum. “Investigation of Bartonella quintana Host Immune Evasion.” 2018. Web. 23 Jan 2021.

Vancouver:

Lambert C. Investigation of Bartonella quintana Host Immune Evasion. [Internet] [Masters thesis]. Victoria University of Wellington; 2018. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/10063/7723.

Council of Science Editors:

Lambert C. Investigation of Bartonella quintana Host Immune Evasion. [Masters Thesis]. Victoria University of Wellington; 2018. Available from: http://hdl.handle.net/10063/7723

Victoria University of Wellington

3. Meijlink, Kimberley Jayne. Can a gut helminth parasite influence Th2 inflammatory responses in the skin?.

Degree: 2017, Victoria University of Wellington

URL: http://hdl.handle.net/10063/6215

► Helminth parasites are one of the most common infectious agents of humans and cause significant health and economic burdens in the countries they are endemic… (more)

▼ Helminth parasites are one of the most common infectious agents of humans and cause significant health and economic burdens in the countries they are endemic in, making elimination an important goal. However, epidemiological studies have suggested an inverse correlation between the incidences of infections by helminth parasites in humans and autoimmune and allergic disease prevalence worldwide; it is thought the eradication of parasites in more affluent countries through improved hygiene is an important factor for the increasing incidence of autoimmune and allergic diseases encountered in the Western world. A Th2 immune response is central in providing immunity against helminth parasites, while suppressing T helper (Th) 1/Th17-mediated inflammation and inducing wound repair mechanisms. Helminths have developed strategies to directly regulate the immune response against them to ensure their own survival. Experimental evidence has demonstrated helminths are also able to dampen inflammatory bystander immune responses in their host, via induction of regulatory mechanisms such as regulatory T cells. These studies have focused primarily on the suppression of food and airway allergies in mouse models and there is limited data on the effect of helminth parasites on skin allergy e.g. atopic dermatitis. Atopic dermatitis (AD) is a chronic/chronically relapsing Th2 inflammatory skin condition, characterized by skin lesions, dry itchy skin and impaired skin barrier function. This is believed to allow the entrance of other allergens into the body more easily, leading to sensitization and initiation of other allergies later in life, a process termed the ‘Allergic March’. With the increased incidence of allergy in the Western world, it is desirable to find new therapies to suppress AD and the onset of the allergic march. During my Masters, I have investigated whether the gut-dwelling mouse parasite Heligmosomoides polygyrus was able to suppress Th2 responses induced in skin tissue using two different allergy models: 1) intradermal injection (ID) of whole mashed-up house dust mite (HDM), which induces Th2 inflammatory responses, and 2) topical application of the chemical hapten dibutyl phthalate-fluorescein isothiocyanate (DBP-FITC), mimicking allergic responses seen in AD. The results show that H. polygyrus induces interleukin (IL)-4 production in tissues distal to the gut, including the ear skin tissue, mainly from cluster of differentiation (CD) 4⁺ T cells. Furthermore, helminth infection was able to suppress Th2-mediated inflammation in the skin in both house dust mite and DBP-FITC models, coinciding with an increase in the proportions of regulatory T cells (Tregs) in skin-associated lymph nodes (LNs). This research further demonstrates the potential use of helminth parasites, or their products, as a therapy for allergic diseases, including those of the skin. Advisors/Committee Members: Le Gros, Graham, Filbey, Kara.

Subjects/Keywords: Allergy; Immunomodulation; Helminth

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APA (6^th Edition):

Meijlink, K. J. (2017). Can a gut helminth parasite influence Th2 inflammatory responses in the skin?. (Masters Thesis). Victoria University of Wellington. Retrieved from http://hdl.handle.net/10063/6215

Chicago Manual of Style (16^th Edition):

Meijlink, Kimberley Jayne. “Can a gut helminth parasite influence Th2 inflammatory responses in the skin?.” 2017. Masters Thesis, Victoria University of Wellington. Accessed January 23, 2021. http://hdl.handle.net/10063/6215.

MLA Handbook (7^th Edition):

Meijlink, Kimberley Jayne. “Can a gut helminth parasite influence Th2 inflammatory responses in the skin?.” 2017. Web. 23 Jan 2021.

Vancouver:

Meijlink KJ. Can a gut helminth parasite influence Th2 inflammatory responses in the skin?. [Internet] [Masters thesis]. Victoria University of Wellington; 2017. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/10063/6215.

Council of Science Editors:

Meijlink KJ. Can a gut helminth parasite influence Th2 inflammatory responses in the skin?. [Masters Thesis]. Victoria University of Wellington; 2017. Available from: http://hdl.handle.net/10063/6215

Georgia Tech

4. Sok, Mary Caitlin P. Immunomodulatory biomaterials to promote early transplant integration and wound healing.

Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2018, Georgia Tech

URL: http://hdl.handle.net/1853/62185

► Ongoing advances in transplantation surgical techniques, together with improvements in immunosuppression regimens, have greatly reduced the rate of postoperative morbidity and graft loss. Despite these… (more)

▼ Ongoing advances in transplantation surgical techniques, together with improvements in immunosuppression regimens, have greatly reduced the rate of postoperative morbidity and graft loss. Despite these advances, wound complications due to systemic immunosuppression are a common post-transplant surgical complication. Therefore, there is a need for therapies that have the ability to allow for wound healing while also preventing rejection without the off-target side effects of systemic immunosuppression. One method that has the potential of mediating these complications is the delivery of immunomodulatory factors that are able to accelerate wound healing and tissue integration through the local recruitment and education of anti-inflammatory, pro-regenerative subsets of immune cells that work to enhance tissue regeneration and alloimmunity by dampening immune activation and cytokine production of factors involved in pathologic inflammation and rejection. We developed a hydrogel-based biomaterial system to deliver Aspirin-Triggered Resolvin D1 and Interleukin-10 in murine models of cutaneous injury and skin transplantation. We demonstrated that injured tissue can be enriched with anti-inflammatory, pro-angiogenic and pro-regenerative populations of neutrophils, monocytes, and macrophages. Dual delivery enhances the presence of tolerogenic dendritic cells and regulatory T cells in skin injury and in transplantation. This research presents a novel immunomodulatory hydrogel system that may aid in soft tissue regeneration by recruiting pro-regenerative immune cell subpopulations and stimulating vascularization after injury. These findings represent an improved understanding of how we may target pro-regenerative cells from different branches of the immune system, and this treatment has the potential to enhance tissue regeneration and prevent wound healing complications after skin tissue injury and lays the foundation for further exploration into the development of local immunomodulatory therapies to prevent graft rejection. Advisors/Committee Members: Botchwey, Edward A. (advisor), Adams, Andrew (committee member), Neish, Andrew (committee member), Babensee, Julia (committee member), Roy, Krishnendu (committee member).

Subjects/Keywords: Biomaterials; Immunoengineering; Immunomodulation; Wound healing

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APA (6^th Edition):

Sok, M. C. P. (2018). Immunomodulatory biomaterials to promote early transplant integration and wound healing. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/62185

Chicago Manual of Style (16^th Edition):

Sok, Mary Caitlin P. “Immunomodulatory biomaterials to promote early transplant integration and wound healing.” 2018. Doctoral Dissertation, Georgia Tech. Accessed January 23, 2021. http://hdl.handle.net/1853/62185.

MLA Handbook (7^th Edition):

Sok, Mary Caitlin P. “Immunomodulatory biomaterials to promote early transplant integration and wound healing.” 2018. Web. 23 Jan 2021.

Vancouver:

Sok MCP. Immunomodulatory biomaterials to promote early transplant integration and wound healing. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1853/62185.

Council of Science Editors:

Sok MCP. Immunomodulatory biomaterials to promote early transplant integration and wound healing. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/62185

University of Otago

5. AlDaif, Basheer. Functional analysis of the Orf virus ORF116 gene: a potential modulator of the interferon response .

Degree: 2014, University of Otago

URL: http://hdl.handle.net/10523/4621

► Orf virus (OV) is the type species of the Parapoxvirus genus. Like other poxviruses, genetic and functional studies have revealed that it has immunomodulatory genes… (more)

▼ Orf virus (OV) is the type species of the Parapoxvirus genus. Like other poxviruses, genetic and functional studies have revealed that it has immunomodulatory genes that manipulate the innate immune response, often during the early stage of infection. The main focus of this study was to find the possible function of a novel gene in OV, ORF116, in strain NZ2 using a microarray approach. The ORF116 gene is 696 nts encoding a predicted polypeptide of 231 aa. Northern blotting analysis and reverse transcription-PCR have shown that ORF116 was expressed early. Northern blotting revealed a transcript of 2.1 kb detected in OV-NZ2 infected cells which could be detected as early as 2 h.p.i. by RT-PCR. The deletion of the ORF116 gene, showed that the virus replicated in primary lamb testis (LT) cells and HeLa cells, indicating that this gene is non-essential in cell culture, although viral growth was reduced in both cell types. Moreover, the deletion mutant produced smaller plaques on LT cells and induced a slower cytopathic effect in HeLa cells. Microarray expression profiling in HeLa-infected cells was conducted to identify genes whose expression altered with the presence of ORF116 and also to analyze the global change in gene expression induced by OV-NZ2 or OV-NZ2Δ116 at early times post-infection. Major findings showed that 3000 and 2200 transcripts were altered in their expression in OV-NZ2- and OV-NZ2Δ116-infected HeLa cells at 6 h.p.i. compared with the mock infection control. Furthermore, two genes IL-6 and IFI16 showed a similar expression pattern of up-regulation and down-regulation respectively relative to mock infection. The analysis of differential cellular gene expression has shown 68 genes differentially expressed at either 4 or 6 h.p.i. Of all of the genes that were analyzed by microarray, IFI44 showed the greatest differential expression between wild type and knockout virus. IFI44 expression was 4.17-fold higher in the knockout compared with the wild type at 4 h.p.i. It was also found that other interferon-stimulated genes were up-regulated to higher levels in the knockout which included RIG-I, MDA5, IFIT2, IFIT1, OAS1, OASL and ISG20. The differential expression of these genes was validated by qRT-PCR which suggests that ORF116 has a role in subverting the interferon (IFN) effector response. This study represents the first functional analysis of ORF116 gene encoded by a parapoxvirus. Advisors/Committee Members: Fleming , Stephen (advisor).

Subjects/Keywords: Orf; virus; ORF116; IFN; Immunomodulation

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APA (6^th Edition):

AlDaif, B. (2014). Functional analysis of the Orf virus ORF116 gene: a potential modulator of the interferon response . (Masters Thesis). University of Otago. Retrieved from http://hdl.handle.net/10523/4621

Chicago Manual of Style (16^th Edition):

AlDaif, Basheer. “Functional analysis of the Orf virus ORF116 gene: a potential modulator of the interferon response .” 2014. Masters Thesis, University of Otago. Accessed January 23, 2021. http://hdl.handle.net/10523/4621.

MLA Handbook (7^th Edition):

AlDaif, Basheer. “Functional analysis of the Orf virus ORF116 gene: a potential modulator of the interferon response .” 2014. Web. 23 Jan 2021.

Vancouver:

AlDaif B. Functional analysis of the Orf virus ORF116 gene: a potential modulator of the interferon response . [Internet] [Masters thesis]. University of Otago; 2014. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/10523/4621.

Council of Science Editors:

AlDaif B. Functional analysis of the Orf virus ORF116 gene: a potential modulator of the interferon response . [Masters Thesis]. University of Otago; 2014. Available from: http://hdl.handle.net/10523/4621

University of Debrecen

6. Zubairu, Mustafa Akan. Phenotypical and functional analysis of vessel wall derived mesenchymal stem cell .

Degree: DE – Általános Orvostudományi Kar, 2014, University of Debrecen

URL: http://hdl.handle.net/2437/194737

► Mesenchymal stem cells, being a unique cell population found in tissue, known for their unique ability to regenerate damaged or lost tissue, have now been… (more)

Subjects/Keywords: Stem cell; Inflammation; Immunomodulation; Immunosuppresion

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APA (6^th Edition):

Zubairu, M. A. (2014). Phenotypical and functional analysis of vessel wall derived mesenchymal stem cell . (Thesis). University of Debrecen. Retrieved from http://hdl.handle.net/2437/194737

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zubairu, Mustafa Akan. “Phenotypical and functional analysis of vessel wall derived mesenchymal stem cell .” 2014. Thesis, University of Debrecen. Accessed January 23, 2021. http://hdl.handle.net/2437/194737.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zubairu, Mustafa Akan. “Phenotypical and functional analysis of vessel wall derived mesenchymal stem cell .” 2014. Web. 23 Jan 2021.

Vancouver:

Zubairu MA. Phenotypical and functional analysis of vessel wall derived mesenchymal stem cell . [Internet] [Thesis]. University of Debrecen; 2014. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/2437/194737.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zubairu MA. Phenotypical and functional analysis of vessel wall derived mesenchymal stem cell . [Thesis]. University of Debrecen; 2014. Available from: http://hdl.handle.net/2437/194737

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Georgia Tech

7. Mokarram-Dorri, Nassir. Modulating immune response inside biomaterial-based nerve conduits to stimulate endogenous peripheral nerve regeneration.

Degree: PhD, Materials Science and Engineering, 2015, Georgia Tech

URL: http://hdl.handle.net/1853/54860

► Injuries to the peripheral nervous system (PNS) are major and common source of disability, impairing the ability to move muscles and/or feel normal sensations, or… (more)

▼ Injuries to the peripheral nervous system (PNS) are major and common source of disability, impairing the ability to move muscles and/or feel normal sensations, or resulting in painful neuropathies. Annually traumatic nerve injuries resulting from collisions, gunshot wounds, fractures, motor vehicle accidents, lacerations, and other forms of penetrating trauma, affected more than 250,000 patients just in the U.S. The clinical gold standard to bridge long non-healing nerve gaps is to use a nerve autograft- typically the patient’s own sural nerve. However, autografts are not ideal because of the need for secondary surgery to ‘source’ the nerve, loss of function at the donor site, lack of appropriate source nerve in diabetic patients, neuroma formation, and the need for multiple graft segments. Despite our best efforts, finding alternative ‘nerve bridges’ for peripheral nerve repair remains challenging – of the four nerve ‘tubes’ FDA approved for use in the clinic, none is typically used to bridge gaps longer than 10 mm due to poor outcomes. Hence, there is a compelling need to design alternatives that match or exceed the performance of autografts across critically sized nerve gaps. Here we demonstrate that early modulation of innate immune response at the site of peripheral nerve injury inside biomaterials-based conduit can favorably bias the endogenous regenerative potential after injury that obviates the need for the downstream modulation of multiple factors and has significant implications for the treatment of long peripheral nerve gaps. Moreover, our study strongly suggests that more than the extent of macrophage presence, their specific phenotype at the site of injury influence the regenerative outcomes. This research will advance our knowledge regarding peripheral nerve regeneration, and help developing technologies that are likely to improve clinical outcomes after peripheral nerve injury. The significant results presented here are complementary to a growing body of evidence showing the direct correlation between macrophage phenotype and the regeneration outcome of injured tissues. Advisors/Committee Members: Bellamkonda, Ravi V. (advisor), Botchwey, Edward A. (committee member), English, Arthur W. (committee member), García, Andrés J. (committee member), Milam, Valeria (committee member).

Subjects/Keywords: Nerve repair; Immunomodulation; Macrophage

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APA (6^th Edition):

Mokarram-Dorri, N. (2015). Modulating immune response inside biomaterial-based nerve conduits to stimulate endogenous peripheral nerve regeneration. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/54860

Chicago Manual of Style (16^th Edition):

Mokarram-Dorri, Nassir. “Modulating immune response inside biomaterial-based nerve conduits to stimulate endogenous peripheral nerve regeneration.” 2015. Doctoral Dissertation, Georgia Tech. Accessed January 23, 2021. http://hdl.handle.net/1853/54860.

MLA Handbook (7^th Edition):

Mokarram-Dorri, Nassir. “Modulating immune response inside biomaterial-based nerve conduits to stimulate endogenous peripheral nerve regeneration.” 2015. Web. 23 Jan 2021.

Vancouver:

Mokarram-Dorri N. Modulating immune response inside biomaterial-based nerve conduits to stimulate endogenous peripheral nerve regeneration. [Internet] [Doctoral dissertation]. Georgia Tech; 2015. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1853/54860.

Council of Science Editors:

Mokarram-Dorri N. Modulating immune response inside biomaterial-based nerve conduits to stimulate endogenous peripheral nerve regeneration. [Doctoral Dissertation]. Georgia Tech; 2015. Available from: http://hdl.handle.net/1853/54860

University of New South Wales

8. Perera, Hettiarachchige. Immunomodulatory approaches for the treatment of neuropathic pain in animal models.

Degree: Medical Sciences, 2016, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/56718 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:41227/SOURCE02?view=true

► Neuropathic pain occurring as a consequence of a disease or lesion in the somatosensory nervous system is devastating and refractory to current treatments. Neuropathic pain… (more)

▼ Neuropathic pain occurring as a consequence of a disease or lesion in the somatosensory nervous system is devastating and refractory to current treatments. Neuropathic pain negatively affects the quality of life of patients and causes an economic burden to the sufferers and the global economy. Thus, there is an overwhelming need to investigate the underlying mechanisms and develop novel treatment approaches. Over the past decade, it has become clear that neuroinflammation plays a critical role in the pathogenesis of neuropathic pain. Indeed, the contribution of leukocytes such as T cells and macrophages, immune-like glial cells such as microglia and astrocytes, and inflammatory cytokines have been implicated in neuropathic pain caused by nervous system injury. Modification of such neuroinflammatory responses via immunomodulation is a potential novel therapeutic approach for the treatment of neuropathic pain.Myelin-derived altered peptide ligands (APLs) generated by transforming the amino acid sequence of native myelin peptides are known to modify immune and inflammatory responses, and are able to inhibit antigen-specific T cell function. APLs have demonstrated promising therapeutic effects in several in vivo and in vitro assays by changing the activation and functions of immune cells, and altering their cytokine profiles. In this thesis, we found that immunisation with the native myelin basic protein (MBP) peptide produced pain hypersensitivity and neuroinflammation in uninjured animals and that co-immunisation with the relevant APL reduced these effects. Next, we showed that immunisation with MBP-derived APL in animals with peripheral nerve injury significantly attenuated pain hypersensitivity and suppressed neuroinflammation, as well as altered some systemic immune responses. However, the same immunisation strategy failed to exert an analgesic effect following spinal cord injury. Lastly, the effects of gene therapy to introduce the anti-inflammatory cytokine interleukin (IL)-35 in the spinal cord were investigated in a mouse model of neuropathic pain. We found that intrathecal administration of a plasmid DNA encoding IL-35 significantly attenuated spinal microglia activation without ameliorating pain hypersensitivity in nerve-injured mice. These findings demonstrate the differential effects of various immunomodulatory approaches and provide important insights into the complexity of immunotherapy for the treatment of diverse neuropathic pain conditions. Advisors/Committee Members: Moalem-Taylor, Gila, Medical Sciences, Faculty of Medicine, UNSW, Carrive, Pascal, Medical Sciences, Faculty of Medicine, UNSW.

Subjects/Keywords: Immunomodulation; Neuropathic pain; Neuroinflammation

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APA (6^th Edition):

Perera, H. (2016). Immunomodulatory approaches for the treatment of neuropathic pain in animal models. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/56718 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:41227/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Perera, Hettiarachchige. “Immunomodulatory approaches for the treatment of neuropathic pain in animal models.” 2016. Doctoral Dissertation, University of New South Wales. Accessed January 23, 2021. http://handle.unsw.edu.au/1959.4/56718 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:41227/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Perera, Hettiarachchige. “Immunomodulatory approaches for the treatment of neuropathic pain in animal models.” 2016. Web. 23 Jan 2021.

Vancouver:

Perera H. Immunomodulatory approaches for the treatment of neuropathic pain in animal models. [Internet] [Doctoral dissertation]. University of New South Wales; 2016. [cited 2021 Jan 23]. Available from: http://handle.unsw.edu.au/1959.4/56718 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:41227/SOURCE02?view=true.

Council of Science Editors:

Perera H. Immunomodulatory approaches for the treatment of neuropathic pain in animal models. [Doctoral Dissertation]. University of New South Wales; 2016. Available from: http://handle.unsw.edu.au/1959.4/56718 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:41227/SOURCE02?view=true

9. Franciele de Cesaro. Evaluation of lymphoproliferative and cytotoxic activities of methanol extracts and fractions from Ipomoea pes-caprae and Vernonia scorpioides.

Degree: 2009, Universidade do Vale do Itajaí

URL: http://www6.univali.br/tede/tde_busca/arquivo.php?codArquivo=661

► As plantas medicinais têm sido alvo de estudo na busca por novos agentes terapêuticos na medicina moderna, incluindo agentes imunomoduladores e antitumorais. O presente estudo… (more)

▼ As plantas medicinais têm sido alvo de estudo na busca por novos agentes terapêuticos na medicina moderna, incluindo agentes imunomoduladores e antitumorais. O presente estudo avaliou o extrato metanólico (EM) e as frações clorofórmio (CLO) e acetato de etila (AE) de Ipomoea pes-caprae e o EM e frações hexano (HEX), diclorometano (DCM) e AE de Vernonia scorpioides quanto à atividade imunomoduladora no teste de linfoproliferação com células esplênicas murinas, estimuladas ou não com fitohemaglutinina (PHA) e quanto à atividade citotóxica em células leucêmicas humanas Jurkat, HL60 e HL60-bcl2. O estudo da atividade imunomodulatória empregou células esplênicas murinas (150.000 células/poço) obtidas pelo rompimento mecânico da cápsula do órgão e incubadas em microplacas de 96 poços a 37 C e 5% de CO2 durante 72 horas com: meio de cultura (controle negativo); PHA (5 μg/mL, controle positivo de proliferação celular); dimetilsulfóxido (DMSO 10%, controle positivo de citotoxicidade); EMs e frações de I. pes-caprae e V. scorpioides (10 μg/mL, 50 μg/mL, 100 μg/mL e 200 μg/mL), isolada e simultaneamente à PHA ou DMSO. A investigação da atividade citotóxica utilizou células leucêmicas humanas (50.000 células/poço) incubadas a 37 C e 5% de CO2 durante 48 horas com: meio de cultura; etoposídeo (10 μM, ETO); DMSO (_0,5%, utilizado como solvente dos EMs e frações); e EMs e frações de I. pes-caprae e V. scorpioides (1μg/mL, 10 μg/mL e 100 μg/mL). A proliferação celular dos ensaios foi quantificada pelo ensaio colorimétrico da redução do MTT (azul de tetrazólio) e expresso em percentagem de crescimento, com os resultados analisados pelos testes Kruskal-Wallis, Mann-Whitney e t não-pareado. A fração CLO de I. pes-caprae mostrou efeito citotóxico nas células esplênicas murinas normais e nas três linhagens de células leucêmicas humanas, enquanto que o EM e a fração AE apresentaram atividade imunoestimuladora nas células normais sem interferir no crescimento das células leucêmicas, sendo a fração AE cerca de 4 vezes mais eficiente (p<0,01). O EM e as frações DCM e HEX de V. scorpioides inibiram a proliferação de células esplênicas murinas e mostraram atividade citotóxica frente às células tumorais, exceto a fração HEX frente às células Jurkat. Nas células normais a atividade citotóxica da fração HEX foi 2 vezes maior que EM e demais frações (p<0,05), enquanto que nas células leucêmicas a fração DCM foi no mínimo 2 vezes mais citotóxica que o EM e demais frações (p<0,05). A fração AE desta espécie mostrou atividade citotóxica seletiva, inibindo o crescimento de células tumorais e estimulando a proliferação das células esplências murinas normais. A superexpressão da proteína bcl2 parece ser modulada por componente(s) presente(s) em ambas as plantas, sugerindo indução de morte celular por apoptose. A continuidade do estudo biomonitorado com as frações de I. pes-caprae e de V. scorpioides permitirá identificar o(s) constituinte(s) responsável(is) pelas atividades imunoestimuladora e citotóxica… Advisors/Committee Members: Alexandre Bella Cruz, Tânia Silvia Fröde, Ednéia Casagranda Bueno.

Subjects/Keywords: cytotoxic activity; immunomodulation; ipomoea; vernonia; FARMACIA; cytotoxic activity; immunomodulation; ipomoea; vernonia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cesaro, F. d. (2009). Evaluation of lymphoproliferative and cytotoxic activities of methanol extracts and fractions from Ipomoea pes-caprae and Vernonia scorpioides. (Thesis). Universidade do Vale do Itajaí. Retrieved from http://www6.univali.br/tede/tde_busca/arquivo.php?codArquivo=661

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Cesaro, Franciele de. “Evaluation of lymphoproliferative and cytotoxic activities of methanol extracts and fractions from Ipomoea pes-caprae and Vernonia scorpioides.” 2009. Thesis, Universidade do Vale do Itajaí. Accessed January 23, 2021. http://www6.univali.br/tede/tde_busca/arquivo.php?codArquivo=661.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Cesaro, Franciele de. “Evaluation of lymphoproliferative and cytotoxic activities of methanol extracts and fractions from Ipomoea pes-caprae and Vernonia scorpioides.” 2009. Web. 23 Jan 2021.

Vancouver:

Cesaro Fd. Evaluation of lymphoproliferative and cytotoxic activities of methanol extracts and fractions from Ipomoea pes-caprae and Vernonia scorpioides. [Internet] [Thesis]. Universidade do Vale do Itajaí; 2009. [cited 2021 Jan 23]. Available from: http://www6.univali.br/tede/tde_busca/arquivo.php?codArquivo=661.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cesaro Fd. Evaluation of lymphoproliferative and cytotoxic activities of methanol extracts and fractions from Ipomoea pes-caprae and Vernonia scorpioides. [Thesis]. Universidade do Vale do Itajaí; 2009. Available from: http://www6.univali.br/tede/tde_busca/arquivo.php?codArquivo=661

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

10. Delahousse, Julia. De l’ifosfamide au géranyloxy-ifosfamide : pharmacomodulation pour cibler et moduler l’immunité : From ifosfamide to geranyloxy-ifosfamide : pharmacomodulation to target and modulate immunity.

Degree: Docteur es, Pharmacotechnie et biopharmacie, 2019, Université Paris-Saclay (ComUE)

URL: http://www.theses.fr/2019SACLS535

►

L’ifosfamide (IFO) est un alkylant de l’ADN de la famille des Oxazaphosphorines, largement utilisé dans divers protocoles de chimiothérapie. Son utilisation en clinique est néanmoins… (more)

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L’ifosfamide (IFO) est un alkylant de l’ADN de la famille des Oxazaphosphorines, largement utilisé dans divers protocoles de chimiothérapie. Son utilisation en clinique est néanmoins limitée en raison d’une néphrotoxicité et une neurotoxicité liées aux métabolites tels que le chloroacétaldéhyde. En effet, l’IFO est une prodrogue présentant un profil pharmacocinétique complexe dont la voie métabolique activatrice est minoritaire et la voie toxicogène majoritaire. La pharmacomodulation chimique est une des stratégies proposées afin de contourner la voie toxicogène et ainsi améliorer son utilisation en clinique. Des analogues de l’IFO (géranyloxy-, farnesyloxy-, squalenyloxy-IFO), capables de s’auto- assembler, ont été développés et les études pharmacologiques ont démontré la preuve de concept de pré-activation de l’IFO. Des optimisations galéniques ont été testées en vue d’une application en pré-clinique puis en clinique. Par ailleurs, la proximité chimique de l’IFO et du cyclophosphamide, nous a conduit à mener des études d’immunomodulation afin d’explorer les propriétés immunomodulatrices de l’IFO et du géranyloxy-IFO et d’ouvrir de nouvelles perspectives dans l’utilisation de ces composés en association avec l’immunothérapie.

Ifosfamide (IFO) is an alkylating agent of the DNA from Oxazaphosphorine family, widely used in various chemotherapy protocols. However, its clinical use is limited due to nephrotoxicity and neurotoxicity related to metabolites such as chloroacetaldehyde. Indeed, IFO is a prodrug characterized by complex pharmacokinetic profile with a minority activating metabolic pathway and a majority toxicogenic pathway. Chemical pharmacomodulation is one of the strategies proposed to bypass the toxicogenic pathway and thus improve its clinical use. IFO analogues (geranyloxy-, farnesyloxy-, squalenyloxy-, squalenyloxy-IFO), able to self-assembly, have been developed and pharmacological studies have demonstrated the proof of concept for the pre-activation of IFO. Galenic optimizations have been tested for pre-clinical and clinical application. In addition, due to the chemical similarity of IFO and cyclophosphamide, immunomodulation studies have been conducted to investigate the immunomodulatory properties of IFO and geranyloxy-IFO with the hope of new perspectives in the use of these compounds in combination with immunotherapy.

Advisors/Committee Members: Paci, Angelo (thesis director).

Subjects/Keywords: Ifosfamide; Géranyloxy-Ifosfamide; Pharmacomodulation; Immunomodulation; Ifosfamide; Geranyloxy-Ifosfamide; Pharmacomodulation; Immunomodulation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Delahousse, J. (2019). De l’ifosfamide au géranyloxy-ifosfamide : pharmacomodulation pour cibler et moduler l’immunité : From ifosfamide to geranyloxy-ifosfamide : pharmacomodulation to target and modulate immunity. (Doctoral Dissertation). Université Paris-Saclay (ComUE). Retrieved from http://www.theses.fr/2019SACLS535

Chicago Manual of Style (16^th Edition):

Delahousse, Julia. “De l’ifosfamide au géranyloxy-ifosfamide : pharmacomodulation pour cibler et moduler l’immunité : From ifosfamide to geranyloxy-ifosfamide : pharmacomodulation to target and modulate immunity.” 2019. Doctoral Dissertation, Université Paris-Saclay (ComUE). Accessed January 23, 2021. http://www.theses.fr/2019SACLS535.

MLA Handbook (7^th Edition):

Delahousse, Julia. “De l’ifosfamide au géranyloxy-ifosfamide : pharmacomodulation pour cibler et moduler l’immunité : From ifosfamide to geranyloxy-ifosfamide : pharmacomodulation to target and modulate immunity.” 2019. Web. 23 Jan 2021.

Vancouver:

Delahousse J. De l’ifosfamide au géranyloxy-ifosfamide : pharmacomodulation pour cibler et moduler l’immunité : From ifosfamide to geranyloxy-ifosfamide : pharmacomodulation to target and modulate immunity. [Internet] [Doctoral dissertation]. Université Paris-Saclay (ComUE); 2019. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2019SACLS535.

Council of Science Editors:

Delahousse J. De l’ifosfamide au géranyloxy-ifosfamide : pharmacomodulation pour cibler et moduler l’immunité : From ifosfamide to geranyloxy-ifosfamide : pharmacomodulation to target and modulate immunity. [Doctoral Dissertation]. Université Paris-Saclay (ComUE); 2019. Available from: http://www.theses.fr/2019SACLS535

11. Belaz, Sorya. Dérivés furanosidiques à visée thérapeutique dans la leishmaniose : caractérisation des effets et mode d'action : Furanosidic derivatives for therapeutic purposes in leishmaniasis, characterization of effects and mode of action.

Degree: Docteur es, Biologie et sciences de la santé, 2017, Rennes 1

URL: http://www.theses.fr/2017REN1B044

►

La leishmaniose est une maladie tropicale négligée pour laquelle l’arsenal thérapeutique actuel est limité. Ce travail de thèse s’est intéressé à rechercher des nouvelles cibles… (more)

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La leishmaniose est une maladie tropicale négligée pour laquelle l’arsenal thérapeutique actuel est limité. Ce travail de thèse s’est intéressé à rechercher des nouvelles cibles thérapeutiques en ciblant la paroi des leishmanies. Le lipophosphoglycane (LPG), constituant majoritaire de la paroi, présente un motif glucidique particulier, le galactofuranose, qui semble une cible thérapeutique intéressante car il est absent des membranes de mammifères. Les galactofuranosyl-transférases sont impliquées dans le métabolisme de ce furanose, et ce travail a débuté par l’étude de ces enzymes et par la caractérisation d’une mutase, également nécessaire au métabolisme du galactofuranose. Une fois les cibles caractérisées dans les 2 stades du parasite, des analogues du galactofuranose ont été testés quant à leur capacité antiparasitaire sur les formes promastigotes et amastigotes de Leishmania donovani. Un composé s’est révélé intéressant et a été plus étudié, le n-octyl-galactofuranose (Galf). Différentes approches ont été utilisées pour caractériser son mode d’action sur les promastigotes et les amastigotes : résonance paramagnétique électronique, microscopie électronique à transmission, cytométrie en flux ou résonance magnétique nucléaire. L’observation d’une activité inductrice du métabolisme oxydatif des macrophages nous a conduits à nous intéresser aux capacités immunomodulatrices de ces analogues galacto-furanosidiques. Ainsi la dernière partie de ce travail est consacrée à l’étude de la polarisation des macrophages par les galactofuranosides, sur un modèle in vitro de macrophages humains. Nous avons pu montrer que le Galf exerçait une activation des macrophages en faveur d’une polarisation de type M1, ce qui pourrait expliquer l’effet limitateur de croissance des amastigotes.

Leishmaniasis is a neglected tropical disease for which the current therapeutic arsenal is limited. This work aimed at finding new therapeutic drugs by targeting the Leishmania cell wall. Lipophosphoglycan (LPG) is the major glycoconjugate in promastigotes cell wall, consisting of a hexasaccharide core including a galactofuranose motif. Galactofuranose is absent in mammalian membranes, thus could be a therapeutic target. First, this work studied the galactofuranosyl-transferases involved in the metabolism of this furanose, as well as a mutase, also necessary for the metabolism of galactofuranose. Once targets were identified in the two parasitic stages, galactofuranose derivatives were tested for antileishmanial activity on promastigotes and amastigotes forms of Leishmania donovani. A compound showed interesting results and has been studied further, the n-octyl-galactofuranose (Galf). Different techniques have been used to characterize its mode of action on promastigotes and amastigotes: electron paramagnetic resonance, transmission electron microscopy, nuclear magnetic resonance or flow cytometry. Infected macrophages treated with Galf were able to produce oxygen derivatives species, leading us to look at the immunomodulatory capacity of Galf…

Advisors/Committee Members: Robert-Gangneux, Florence (thesis director), Gangneux, Jean-Pierre (thesis director).

Subjects/Keywords: Galactofuranoside; Leishmania; Invertase; Immunomodulation; Galactofuranoside; Leishmania; Invertase; Immunomodulation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Belaz, S. (2017). Dérivés furanosidiques à visée thérapeutique dans la leishmaniose : caractérisation des effets et mode d'action : Furanosidic derivatives for therapeutic purposes in leishmaniasis, characterization of effects and mode of action. (Doctoral Dissertation). Rennes 1. Retrieved from http://www.theses.fr/2017REN1B044

Chicago Manual of Style (16^th Edition):

Belaz, Sorya. “Dérivés furanosidiques à visée thérapeutique dans la leishmaniose : caractérisation des effets et mode d'action : Furanosidic derivatives for therapeutic purposes in leishmaniasis, characterization of effects and mode of action.” 2017. Doctoral Dissertation, Rennes 1. Accessed January 23, 2021. http://www.theses.fr/2017REN1B044.

MLA Handbook (7^th Edition):

Belaz, Sorya. “Dérivés furanosidiques à visée thérapeutique dans la leishmaniose : caractérisation des effets et mode d'action : Furanosidic derivatives for therapeutic purposes in leishmaniasis, characterization of effects and mode of action.” 2017. Web. 23 Jan 2021.

Vancouver:

Belaz S. Dérivés furanosidiques à visée thérapeutique dans la leishmaniose : caractérisation des effets et mode d'action : Furanosidic derivatives for therapeutic purposes in leishmaniasis, characterization of effects and mode of action. [Internet] [Doctoral dissertation]. Rennes 1; 2017. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2017REN1B044.

Council of Science Editors:

Belaz S. Dérivés furanosidiques à visée thérapeutique dans la leishmaniose : caractérisation des effets et mode d'action : Furanosidic derivatives for therapeutic purposes in leishmaniasis, characterization of effects and mode of action. [Doctoral Dissertation]. Rennes 1; 2017. Available from: http://www.theses.fr/2017REN1B044

12. Anielle Torres de Melo. Efeitos da imunomodulaÃÃo em animais sobreviventes de Sepse grave sobre as alteraÃÃes inflamatÃrias observadas na mucosite intestinal induzida por irinotecano.

Degree: Master, 2014, Universidade Federal do Ceará

URL: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13069 ;

► O cÃncer colorretal (CCR) Ã um dos mais comuns tumores malignos atualmente. Regimes Ã base de irinotecano (IRI) tÃm sido utilizados no tratamento do CCR… (more)

▼ O cÃncer colorretal (CCR) Ã um dos mais comuns tumores malignos atualmente. Regimes Ã base de irinotecano (IRI) tÃm sido utilizados no tratamento do CCR e do CCR metastÃtico. Contudo, tais regimes estÃo associados ao surgimento de mucosite intestinal (MI), muitas vezes limitante do tratamento. A MI e a diarrÃia grave sÃo efeitos colaterais frequentes que podem atingir de 15-25% dos pacientes em quimioterapia. No entanto, o manejo clÃnico destes efeitos secundÃrios ainda Ã parcialmente ineficaz. O estudo dos mecanismos e mediadores envolvidos na resposta imune no estado de pÃs sepse vem evidenciando que nesta condiÃÃo parece haver uma inibiÃÃo de eventos inflamatÃrios entre os quais a migraÃÃo de neutrÃfilos. Dessa forma, o estado de pÃs-sepse poderia interferir no curso da MI induzida por IRI. Pretende-se avaliar os efeitos da imunomodulaÃÃo em animais sobreviventes de sepse grave no desenvolvimento das alteraÃÃes inflamatÃrias da MI induzida pelo IRI. Camundongos C57BL/6 machos, 20-25g, foram divididos em 4 grupos (n=5-8), submetidos ao modelo de ligaÃÃo e perfuraÃÃo do ceco (CLP) e tratados com ertapenem 20mg/Kg i.p. 6h depois da CLP e de 12/12h por trÃs dias, para induzir aproximadamente 50% de sobrevida. Animais submetidos Ã cirurgia mas nÃo Ã perfuraÃÃo do ceco (SHAM) receberam soluÃÃo salina (Sal, 5 mL/Kg, i.p.). Quinze dias apÃs CLP, os animais sobreviventes e animais do grupo SHAM receberam soluÃÃo salina (Sal, 5 ml/Kg, i.p.) durante 4 dias ou IRI (75mg/kg, i.p.). A massa corpÃrea (g) foi mensurada diariamente. No 5Â ou 7 Â dia, foi avaliada a contagem total de leucÃcitos (x103/ÂL) e a diarreia (escores). ApÃs a morte, o jejuno e o Ãleo foram recolhidos para a dosagem da mieloperoxidase (MPO), IL-1β e IL-10 (pg/mL) e anÃlise histopatolÃgica, ANOVA/Bonferroni ou Kruskal Wallis/Dunn foram usados como testes estatÃsticos. P <0,05 foi aceito. Protocolo CEPA 84̸ 2014. Animais pÃs-sÃpticos por CLP tratados com IRI apresentaram reduÃÃo dos escores de diarreia e atividade da MPO no 5Â e 7Â dia (diarreia 5D: [0(0-0)]; 7D: [0(0-2) / MPO do jejuno e Ãleo, 5D: 2,96Â1,01; 2,35Â0,76 e 7D:0,42Â0,14; 0,92Â0,19, respectivamente) quando comparados com os animais SHAM tratados com IRI (diarreia 5D: 1[0-1]; 7D:[2,5(1-3)] /MPO do jejuno e Ãleo, 5D: 8,16Â1,48; 7,96Â0,96; 7D: 2,51Â0,67; 2,87Â0,65, respectivamente). AlÃm disso, animais pÃs-sÃpticos tratados com IRI apresentaram reduÃÃo nos danos histopatolÃgicos no 5Â e 7Â dia (5D no jejuno e Ãleo: [1(1â3)] e [1(0-1)]; e 7D no Ãleo: [2(1-3)] em relaÃÃo a IRI (5D no jejuno e Ãleo: [4(2-4)] e [4(1-4)] / 7D: Ãleo [4(3-4)]) e aumento dos nÃveis da citocina IL-10 (5D no jejuno e Ãleo: 55,80Â 3,42; 34,45Â1,87; 7D: Ãleo: 133,00Â20,25) em comparaÃÃo com SHAM + IRI (5D no jejuno e Ãleo: 34,45Â1,87; 6,91Â 3,05; 7D no Ãleo: 63,67Â 9,08). No entanto, animais CLP + IRI nÃo tiveram alteraÃÃo da leucopenia induzida por IRI. Animais C57BL/6 pÃs-sÃpticos apresentaram reduÃÃo da lesÃo da mucosa intestinal e infiltraÃÃo de neutrÃfilos na MI induzida por IRI. Tal efeito pode ser… Advisors/Committee Members: Pedro Marcos Gomes Soares, Lilia Maria Carneiro CÃmara, Ronaldo de Albuquerque Ribeiro.

Subjects/Keywords: FARMACOLOGIA; Mucosite; Sepse; ImunomodulaÃÃo; Mucositis; Sepsis; Immunomodulation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Melo, A. T. d. (2014). Efeitos da imunomodulaÃÃo em animais sobreviventes de Sepse grave sobre as alteraÃÃes inflamatÃrias observadas na mucosite intestinal induzida por irinotecano. (Masters Thesis). Universidade Federal do Ceará. Retrieved from http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13069 ;

Chicago Manual of Style (16^th Edition):

Melo, Anielle Torres de. “Efeitos da imunomodulaÃÃo em animais sobreviventes de Sepse grave sobre as alteraÃÃes inflamatÃrias observadas na mucosite intestinal induzida por irinotecano.” 2014. Masters Thesis, Universidade Federal do Ceará. Accessed January 23, 2021. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13069 ;.

MLA Handbook (7^th Edition):

Melo, Anielle Torres de. “Efeitos da imunomodulaÃÃo em animais sobreviventes de Sepse grave sobre as alteraÃÃes inflamatÃrias observadas na mucosite intestinal induzida por irinotecano.” 2014. Web. 23 Jan 2021.

Vancouver:

Melo ATd. Efeitos da imunomodulaÃÃo em animais sobreviventes de Sepse grave sobre as alteraÃÃes inflamatÃrias observadas na mucosite intestinal induzida por irinotecano. [Internet] [Masters thesis]. Universidade Federal do Ceará 2014. [cited 2021 Jan 23]. Available from: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13069 ;.

Council of Science Editors:

Melo ATd. Efeitos da imunomodulaÃÃo em animais sobreviventes de Sepse grave sobre as alteraÃÃes inflamatÃrias observadas na mucosite intestinal induzida por irinotecano. [Masters Thesis]. Universidade Federal do Ceará 2014. Available from: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=13069 ;

13. LUNDAHL, MIMMI LOUISE. The immunomodulatory properties of L-rhamnose.

Degree: School of Biochemistry & Immunology. Discipline of Biochemistry, 2020, Trinity College Dublin

URL: http://hdl.handle.net/2262/92870

► L-Rhamnose is a non-mammalian monosaccharide ubiquitously found on the surface of both commensal and pathogenic bacteria. Previous publications had identified that L-rhamnose-rich Mycobacterium tuberculosis glycolipids,… (more)

Subjects/Keywords: Immunomodulation; Carbohydrates; Macrophages; Tuberculosis; Innate Memory

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

LUNDAHL, M. L. (2020). The immunomodulatory properties of L-rhamnose. (Thesis). Trinity College Dublin. Retrieved from http://hdl.handle.net/2262/92870

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

LUNDAHL, MIMMI LOUISE. “The immunomodulatory properties of L-rhamnose.” 2020. Thesis, Trinity College Dublin. Accessed January 23, 2021. http://hdl.handle.net/2262/92870.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

LUNDAHL, MIMMI LOUISE. “The immunomodulatory properties of L-rhamnose.” 2020. Web. 23 Jan 2021.

Vancouver:

LUNDAHL ML. The immunomodulatory properties of L-rhamnose. [Internet] [Thesis]. Trinity College Dublin; 2020. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/2262/92870.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

LUNDAHL ML. The immunomodulatory properties of L-rhamnose. [Thesis]. Trinity College Dublin; 2020. Available from: http://hdl.handle.net/2262/92870

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Brunel University

14. Sumner, Rachel Clair. The role of hemispheric lateralisation in immunity & human immunodeficiency virus Type 1 (HIV-1).

Degree: PhD, 2012, Brunel University

URL: http://bura.brunel.ac.uk/handle/2438/7023 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558998

► Neuromodulation of the immune system has been described to be influenced by hemispheric lateralisation (HL), the stable tendency to relatively utilise one hemisphere or its… (more)

▼ Neuromodulation of the immune system has been described to be influenced by hemispheric lateralisation (HL), the stable tendency to relatively utilise one hemisphere or its functions over another. To date there has not been a systematic review of research in this phenomenon conducted, and only one study has examined the effects of HL on the progression of a disease – Human Immunodeficiency Virus (HIV). That research was conducted on a small sample with little control for confounders. The present work sought to compile a systematic review of literature concerning HL and immunity in humans, using effect size analysis. Further, the present work also describes an empirical advancement of this earlier HIV study with stricter control over confounds in a larger sample. The findings corroborated the theory of asymmetrical immune influence by HL via the systematic review showing clear, relatively consistent and strong relationships between left-HL and immunopotentiation. The empirical prospective study extended current knowledge of this relationship in HIV to identify a moderator – HAART treatment. Specifically, left-HL predicted better immunity in HIV-1 patients independent of confounders, with further findings of the same pattern in untreated patients, but not in HAART-treated patients. Further observations were made between HL and HIV-relevant behaviours, again adding to current knowledge. The finding of left-HL being associated with fewer sexual partners in Europeans presents new information of relevance to public health. The combined findings of the present work suggest that left-HL has predictive value in illness (HIV-1) and in general immunity. The present work adds to the existing knowledge new information concerning a moderating factor of the HLimmunity relationship in HIV, and behavioural implications of HL which impact upon HIV disease. Potential explanations for moderation, proposals for neurobiological mechanisms and direction towards future, more rigourous study in the field, both in HIV and immunity, are discussed.

Subjects/Keywords: 610; Hemispheric lateralisation; Neuroimmunology; Immunity; Immunomodulation

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APA (6^th Edition):

Sumner, R. C. (2012). The role of hemispheric lateralisation in immunity & human immunodeficiency virus Type 1 (HIV-1). (Doctoral Dissertation). Brunel University. Retrieved from http://bura.brunel.ac.uk/handle/2438/7023 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558998

Chicago Manual of Style (16^th Edition):

Sumner, Rachel Clair. “The role of hemispheric lateralisation in immunity & human immunodeficiency virus Type 1 (HIV-1).” 2012. Doctoral Dissertation, Brunel University. Accessed January 23, 2021. http://bura.brunel.ac.uk/handle/2438/7023 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558998.

MLA Handbook (7^th Edition):

Sumner, Rachel Clair. “The role of hemispheric lateralisation in immunity & human immunodeficiency virus Type 1 (HIV-1).” 2012. Web. 23 Jan 2021.

Vancouver:

Sumner RC. The role of hemispheric lateralisation in immunity & human immunodeficiency virus Type 1 (HIV-1). [Internet] [Doctoral dissertation]. Brunel University; 2012. [cited 2021 Jan 23]. Available from: http://bura.brunel.ac.uk/handle/2438/7023 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558998.

Council of Science Editors:

Sumner RC. The role of hemispheric lateralisation in immunity & human immunodeficiency virus Type 1 (HIV-1). [Doctoral Dissertation]. Brunel University; 2012. Available from: http://bura.brunel.ac.uk/handle/2438/7023 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558998

University of Toronto

15. Prodeus, Aaron. Targeting IgV-like Domain Immune Checkpoint Receptors with Novel Nucleic Acid and Protein-Based Therapeutics.

Degree: PhD, 2018, University of Toronto

URL: http://hdl.handle.net/1807/89699

► The immune system is heavily regulated by negative checkpoint pathways; a network of cell signaling events governed by immune inhibitory ligand-receptor interactions. Physiologically, these negative… (more)

▼ The immune system is heavily regulated by negative checkpoint pathways; a network of cell signaling events governed by immune inhibitory ligand-receptor interactions. Physiologically, these negative checkpoint pathways are crucial for maintenance of self-tolerance in peripheral tissues. These pathways are often usurped by tumors as a mechanism to dampen anti-tumor immune responses. Clinically, the targeted blockade of PD-1:PD-L1 and CTLA-4:CD80/86 checkpoint ligand-receptor interactions using monoclonal antibodies has proved to be a viable means to provoke effective and durable anti-tumor responses. Conversely, agonists that stimulate these natural immunoinhibitory signaling pathways could potentially serve as immune-suppressants for treating patients with inflammatory and autoimmune disorders. The central theme of this thesis was to derive novel biotherapeutics that agonize or antagonize clinically-relevant checkpoint receptors. Specifically, the thesis focuses largely on targeting checkpoint receptors with short, single-stranded oligonucleotides, termed DNA aptamers, which bind molecular targets with affinity and specificity rivalling that of monoclonal antibodies. As a proof-of-principle, I first describe the derivation of DNA aptamers which bind to murine PD-1 and antagonize the PD-1:PD-L1 pathway to release anti-tumor immune responses and suppress the growth of a murine colon carcinoma tumor implant in-vivo. Second, I report the development of aptamers that bind to CD200R1 and agonize this inhibitory receptor. Strikingly, these anti-CD200R1 agonists were found to act as strong immunosuppressant’s in mouse models of transplant rejection and allergy. Lastly, I described the engineering of a novel multimeric fusion protein, consisting of the extracellular IgV-like domain of the checkpoint ligand VISTA, fused to a short helical pentamerization domain derived from the cartilage oligomeric matrix protein. This soluble agonist readily inhibited T-cell activation in-vitro, and suppressed inflammation in models of transplant rejection and autoimmune hepatitis. Notably, this construct represents the first agonist targeting the as-of-yet discovered VISTA-receptor to stimulate immunoinhibitory signaling in-vivo. Advisors/Committee Members: Gariepy, Jean, Medical Biophysics.

Subjects/Keywords: Aptamer; Autoimmunity; Immunomodulation; Immunotherapy; Inflammation; Oncology; 0307

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APA (6^th Edition):

Prodeus, A. (2018). Targeting IgV-like Domain Immune Checkpoint Receptors with Novel Nucleic Acid and Protein-Based Therapeutics. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/89699

Chicago Manual of Style (16^th Edition):

Prodeus, Aaron. “Targeting IgV-like Domain Immune Checkpoint Receptors with Novel Nucleic Acid and Protein-Based Therapeutics.” 2018. Doctoral Dissertation, University of Toronto. Accessed January 23, 2021. http://hdl.handle.net/1807/89699.

MLA Handbook (7^th Edition):

Prodeus, Aaron. “Targeting IgV-like Domain Immune Checkpoint Receptors with Novel Nucleic Acid and Protein-Based Therapeutics.” 2018. Web. 23 Jan 2021.

Vancouver:

Prodeus A. Targeting IgV-like Domain Immune Checkpoint Receptors with Novel Nucleic Acid and Protein-Based Therapeutics. [Internet] [Doctoral dissertation]. University of Toronto; 2018. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1807/89699.

Council of Science Editors:

Prodeus A. Targeting IgV-like Domain Immune Checkpoint Receptors with Novel Nucleic Acid and Protein-Based Therapeutics. [Doctoral Dissertation]. University of Toronto; 2018. Available from: http://hdl.handle.net/1807/89699

University of Toronto

16. Mak, Alastair. Investigation of the Mechanism of Idiosyncratic Drug-Induced Liver Injury by Immune System Modulation.

Degree: PhD, 2018, University of Toronto

URL: http://hdl.handle.net/1807/89812

► Idiosyncratic drug-induced liver injury (IDILI) continues to be an important issue. There is increasing clinical evidence that most IDILI is immune mediated. Extensive mechanistic studies… (more)

▼ Idiosyncratic drug-induced liver injury (IDILI) continues to be an important issue. There is increasing clinical evidence that most IDILI is immune mediated. Extensive mechanistic studies are needed to better understand these reactions; however, it is impossible to do controlled experiments in humans, and previous animal models did not properly model IDILI. If IDILI is immune mediated, and the major factor preventing liver injury in patients is immune tolerance, then a plausible method to develop an animal model of IDILI would be to impair immune tolerance. Therefore, the objectives of my research were to develop a valid animal model of IDILI, use this model to test mechanistic hypotheses, and to develop better ways to predict risk. In my first two papers I show that immunization of mice with drug-modified hepatic proteins prior to drug exposure paradoxically decreased liver injury unless immune tolerance was impaired during the immunization. In my third paper, I show that PD1-/- mice treated with anti- CTLA-4 and amodiaquine can lead to significant liver injury and liver dysfunction, which is mediated by CD8 T cells. In my fourth paper, I show that this impaired immune tolerance model is able to unlock the potential of isoniazid and nevirapine to cause increased liver injury. Finally, in my fifth paper, I show that this impaired immune tolerance model is also able to distinguish the potential for liver injury of chemically similar drugs, where one drug causes IDILI in humans and the other does not (troglitazone/pioglitazone and tolcapone/entacapone). Overall, I have shown that risk of developing IDILI may be influenced by previous exposures, and I have further developed a model of IDILI, showing its potential for other drugs and as a tool for drug screening. Further characterization and validation of these models is required; however, it is likely that they will make it possible to perform mechanistic studies that have been impossible in the past. Advisors/Committee Members: Uetrecht, Jack, Pharmaceutical Sciences.

Subjects/Keywords: Animal Models; Idiosyncratic Drug Reactions; Immunomodulation; 0383

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APA (6^th Edition):

Mak, A. (2018). Investigation of the Mechanism of Idiosyncratic Drug-Induced Liver Injury by Immune System Modulation. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/89812

Chicago Manual of Style (16^th Edition):

Mak, Alastair. “Investigation of the Mechanism of Idiosyncratic Drug-Induced Liver Injury by Immune System Modulation.” 2018. Doctoral Dissertation, University of Toronto. Accessed January 23, 2021. http://hdl.handle.net/1807/89812.

MLA Handbook (7^th Edition):

Mak, Alastair. “Investigation of the Mechanism of Idiosyncratic Drug-Induced Liver Injury by Immune System Modulation.” 2018. Web. 23 Jan 2021.

Vancouver:

Mak A. Investigation of the Mechanism of Idiosyncratic Drug-Induced Liver Injury by Immune System Modulation. [Internet] [Doctoral dissertation]. University of Toronto; 2018. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1807/89812.

Council of Science Editors:

Mak A. Investigation of the Mechanism of Idiosyncratic Drug-Induced Liver Injury by Immune System Modulation. [Doctoral Dissertation]. University of Toronto; 2018. Available from: http://hdl.handle.net/1807/89812

Clemson University

17. Houke, Haley R. Effects of the Indirubin Derivative E804 on Glioblastoma Associated Immunomodulation.

Degree: MS, Biological Sciences, 2016, Clemson University

URL: https://tigerprints.clemson.edu/all_theses/2404

► Glioblastomas are the most common malignant brain tumor, with an annual incidence of 6 in 100,000 people. Conventional treatment modalities, including chemotherapy and radiation, are… (more)

▼ Glioblastomas are the most common malignant brain tumor, with an annual incidence of 6 in 100,000 people. Conventional treatment modalities, including chemotherapy and radiation, are toxic and cause a decrease in quality of life as the disease progresses. Several investigators have turned to pharmacologically active derivatives of herbal remedies as less-toxic alternatives. Indirubin, a dark red isomer of indigo, is known to be effective in treating chronic inflammation and some forms of cancer, and the mechanism is, in part, due to activity as a ligand for the transcription factor aryl hydrocarbon receptor (AhR). As with most AhR ligands, indirubin induces the CYP1 family of metabolizing enzymes, alters cell cycling, and can be active through the GSK-3Î² pathway. In recent years, bioavailable derivatives have been synthesized, including indirubin-3'-(2,3 dihydroxy-propyl)-oximether (E804). Several lines of research show that E804 has anti-angiogenic and anti-proliferative properties, and we previously demonstrated anti-inflammatory properties of E804. In this study, T98G human glioblastoma cells were treated with E804 to determine the degree of AhR activation, the secretion of both immunosuppressive and pro-inflammatory cytokines by the tumor cells, and the effects of those tumor secretions on macrophage polarization. E804 is potent inducer of CYP1B1 in T98G cells, has modest effects on TGFÎ²2 secretion, and suppresses VEGF at high does, while enhancing VEGF secretion at low doses. The secretion of IL-6 by T98G cells was only modestly affected at the highest treatment levels. The effects of supernatants derived from E804-treated T98G cells on macrophage indicate that E804 may polarize macrophages to the pro-tumor M2 phenotype. Overall, the results of this study indicate that E804 concentrations would need to be carefully monitored in a clinical application. Future studies should include an in vivo model of brain tumors to test the potential of E804 as a standalone, or adjuvant treatment for glioblastoma. Advisors/Committee Members: Charles D. Rice, PhD, Committee Chair, Yanzhang Wei, PhD, Vincent S. Gallicchio, PhD.

Subjects/Keywords: Cancer; E804; Glioblastoma; Immunology; Immunomodulation; Indirubin

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APA (6^th Edition):

Houke, H. R. (2016). Effects of the Indirubin Derivative E804 on Glioblastoma Associated Immunomodulation. (Masters Thesis). Clemson University. Retrieved from https://tigerprints.clemson.edu/all_theses/2404

Chicago Manual of Style (16^th Edition):

Houke, Haley R. “Effects of the Indirubin Derivative E804 on Glioblastoma Associated Immunomodulation.” 2016. Masters Thesis, Clemson University. Accessed January 23, 2021. https://tigerprints.clemson.edu/all_theses/2404.

MLA Handbook (7^th Edition):

Houke, Haley R. “Effects of the Indirubin Derivative E804 on Glioblastoma Associated Immunomodulation.” 2016. Web. 23 Jan 2021.

Vancouver:

Houke HR. Effects of the Indirubin Derivative E804 on Glioblastoma Associated Immunomodulation. [Internet] [Masters thesis]. Clemson University; 2016. [cited 2021 Jan 23]. Available from: https://tigerprints.clemson.edu/all_theses/2404.

Council of Science Editors:

Houke HR. Effects of the Indirubin Derivative E804 on Glioblastoma Associated Immunomodulation. [Masters Thesis]. Clemson University; 2016. Available from: https://tigerprints.clemson.edu/all_theses/2404

University of Sydney

18. Sekhon, Bhagwant Kaur. Immunomodulation of Traditional Chinese Medicines: Applications and Implications for Cancer Medicine .

Degree: 2016, University of Sydney

URL: http://hdl.handle.net/2123/16278

► As cancer continues to be one of the leading causes of death in Australia and worldwide, with an ageing population it is likely that malignancy… (more)

Subjects/Keywords: Cancer; glycoprotein; herbal medicine; immunomodulation; polysaccharopeptide; Astragalus

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APA (6^th Edition):

Sekhon, B. K. (2016). Immunomodulation of Traditional Chinese Medicines: Applications and Implications for Cancer Medicine . (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/16278

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sekhon, Bhagwant Kaur. “Immunomodulation of Traditional Chinese Medicines: Applications and Implications for Cancer Medicine .” 2016. Thesis, University of Sydney. Accessed January 23, 2021. http://hdl.handle.net/2123/16278.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sekhon, Bhagwant Kaur. “Immunomodulation of Traditional Chinese Medicines: Applications and Implications for Cancer Medicine .” 2016. Web. 23 Jan 2021.

Vancouver:

Sekhon BK. Immunomodulation of Traditional Chinese Medicines: Applications and Implications for Cancer Medicine . [Internet] [Thesis]. University of Sydney; 2016. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/2123/16278.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sekhon BK. Immunomodulation of Traditional Chinese Medicines: Applications and Implications for Cancer Medicine . [Thesis]. University of Sydney; 2016. Available from: http://hdl.handle.net/2123/16278

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of New South Wales

19. Whittall, Christine. Interaction between N-(3-oxododecanoyl)-L-homoserine lactone and peroxisome proliferator-activated receptor gamma.

Degree: Biotechnology & Biomolecular Sciences, 2009, University of New South Wales

URL: http://handle.unsw.edu.au/1959.4/44957 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:8254/SOURCE02?view=true

► Pseudomonas aeruginosa is a significant pathogen of immunocompromised individuals, and the main mechanism by which it mediates virulence is through the coordination of gene expression… (more)

▼ Pseudomonas aeruginosa is a significant pathogen of immunocompromised individuals, and the main mechanism by which it mediates virulence is through the coordination of gene expression by an intricate quorum sensing system. One of the signalling molecules of this system, N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) has been shown to have immunomodulatory capabilities, discrete to its quorum sensing role.While the general focus of research in this area is on the physiological outcomes of this interaction on cell function, there is currently little concrete evidence identifying the receptor(s) for OdDHL in mammalian cells, and hence the biochemical mechanism behind the immunomodulation caused by OdDHL remains largely unknown. This study identifies peroxisome proliferator-activated receptor γ (PPARγ) as a mammalian target for OdDHL. PPARγ is a mammalian transcription factor involved in fatty acid metabolism and is heavily involved in the inflammatory response, being a negative regulator of inflammation.It is shown here that OdDHL is able to instigate signalling through PPARγ by activation of the ligand binding domain (LBD), suggesting that OdDHL may act as a PPARγ agonist. OdDHL is able to compete with the PPARγ agonist, rosiglitazone, causing a relative antagonism of PPARγ activity when given in tandem with the agonist. The bacterial signalling molecule is unable to displace the irreversible PPARγ antagonist GW9662. This effect on PPARγ is specific to OdDHL, as the smaller P. aeruginosa signalling molecule, N-butyryl-L-homoserine lactone had no significant effect on PPARγ activation.In order to confirm PPARγ as a putative receptor for OdDHL in mammalian cells, initial experiments were undertaken to optimise conditions to produce PPARγ LBD protein for binding interaction studies. The fidelity of the protein sequence was established and expression of the protein in an appropriate vector was confirmed. The protein produced was insoluble and hence not functional for binding studies, suggesting that additional optimisation of expression conditions, or manipulation and refolding of the protein is necessary before further experimentation can take place.The identification of PPARγ as a receptor for OdDHL in mammalian cells is an important step in understanding the nature and scope of the interaction between OdDHL and host cell physiology, especially the significance of this interaction during P. aeruginosa infection. Continuation of this research, in particular completion of protein-ligand binding studies between OdDHL and PPARγ has the potential to clarify the significance of the immunomodulation caused by OdDHL, while providing us with a platform from which we may exploit it.

Subjects/Keywords: Immunomodulation; OdDHL; PPAR

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Whittall, C. (2009). Interaction between N-(3-oxododecanoyl)-L-homoserine lactone and peroxisome proliferator-activated receptor gamma. (Masters Thesis). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/44957 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:8254/SOURCE02?view=true

Chicago Manual of Style (16^th Edition):

Whittall, Christine. “Interaction between N-(3-oxododecanoyl)-L-homoserine lactone and peroxisome proliferator-activated receptor gamma.” 2009. Masters Thesis, University of New South Wales. Accessed January 23, 2021. http://handle.unsw.edu.au/1959.4/44957 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:8254/SOURCE02?view=true.

MLA Handbook (7^th Edition):

Whittall, Christine. “Interaction between N-(3-oxododecanoyl)-L-homoserine lactone and peroxisome proliferator-activated receptor gamma.” 2009. Web. 23 Jan 2021.

Vancouver:

Whittall C. Interaction between N-(3-oxododecanoyl)-L-homoserine lactone and peroxisome proliferator-activated receptor gamma. [Internet] [Masters thesis]. University of New South Wales; 2009. [cited 2021 Jan 23]. Available from: http://handle.unsw.edu.au/1959.4/44957 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:8254/SOURCE02?view=true.

Council of Science Editors:

Whittall C. Interaction between N-(3-oxododecanoyl)-L-homoserine lactone and peroxisome proliferator-activated receptor gamma. [Masters Thesis]. University of New South Wales; 2009. Available from: http://handle.unsw.edu.au/1959.4/44957 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:8254/SOURCE02?view=true

20. Rosa do carmo, Fillipe Luiz. La protéine de couche de surface SlpB assure la médiation de l’immunomodulation et de l’adhésion chez le probiotique Propionibacterium freudenreichii CIRM-BIA 129. : Surface layer protein SlpB mediates immunodulation and adhesion in the probiotic Propionibacterium freudenreichii CIRM-BIA 129.

Degree: Docteur es, Sciences de l'aliment, 2018, Rennes, Agrocampus Ouest; UNIVERSIDADEFEDERALDEMINASGERAIS, UFMG

URL: http://www.theses.fr/2018NSARB315

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Propionibacterium freudenreichii est une bactérie Gram-positive bénéfique, traditionnellement utilisée comme levain d’affinage fromager, qui bénéficie du statut GRAS (Generally Recognized As Safe). P. freudenreichii a… (more)

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Propionibacterium freudenreichii est une bactérie Gram-positive bénéfique, traditionnellement utilisée comme levain d’affinage fromager, qui bénéficie du statut GRAS (Generally Recognized As Safe). P. freudenreichii a révélé un effet immunomodulateur qui a été confirmé in vivo par la capacité à protéger des souris d’une colite aigüe induite. L’effet anti-inflammatoire est cependant hautement souche-dépendant. Il est dû, au moins en partie, à des composés de surface clés qui favorisent ces effets probiotiques. Les bactéries Gram-positives, y compris P. freudenreichii, peuvent être recouvertes d’une couche extérieure protéique, appelée « surface-layer », paracristalline, et formée par l’autoassemblage de protéines dites de S-layer (Slps). Les Slps, dans différentes bactéries, sont impliquées dans plusieurs caractéristiques probiotiques, telles que l’adhésion aux cellules de l’hôte et au mucus, la persistance dans l’intestin, ou encore l’immunomodulation. Le but de cette étude est d’étudil’immunomodulation. Le but de cette étude est d’étudier, chez une souche probiotique de P. freudenreichii, la protéine de surface qui joue le principal rôle dans les interactions probiotiques avec l’hôte. La souche P. freudenreichii CIRM-BIA 129, récemment reconnue comme immunomodulatrice prometteuse, possède plusieurs protéines de surface Slps, y compris SlpB. Dans la présente étude, l’inactivation du gène correspondant, dans la souche mutante CB129¿slpB, a provoqué une baisse drastique de l’adhésion aux cellules intestinales épithéliales HT-29, confirmant le rôle clé des Slps dans l’adhési

Propionibacterium freudenreichii is a beneficial Gram-positive bacterium, traditionally used as a cheese ripening starter, with the GRAS status (Generally Recognized As Safe). P. freudenreichii has revealed an immunomodulatory effect confirmed in vivo by the ability to protect mice from induced acute colitis. The anti-inflammatory effect is however highly strain-dependent and due, at least in part, to key surface compounds favouring probiotic effects. Gram-positive bacteria, including P. freudenreichii, can be covered with an external proteinaceous layer called a surface-layer paracrystalin layer and formed by the self-assembly of surface-layer-proteins (Slps). Slps were shown, in different bacteria, to be involved in several probiotics traits, such as adhesion to host cells and mucus, persistence within the gut, or immunomodulation. The aim of this study is to investigate, in a P. freudenreichii probiotic strain, the surface protein that plays the main role in the probioticinteraction with the host. The P. freudenreichii CIRM-BIA 129 strain recently revealed promising immunomodulatory properties and possesses several Slps, including SlpB. In the presented work, inactivation of the corresponding gene, CB129¿slpBa mutant strain, caused a drastic decrease in adhesion to intestinal epithelial HT-29 cells, further evidencing the key role of Slps in cell adhesion. we investigated immune response of HT-29 cells towards P. freudenreichii CIRM-BIA 129…

Advisors/Committee Members: Jan, Gwenaël (thesis director), Azevedo, Vasco (thesis director).

Subjects/Keywords: Propionibactéries; Probiotique; Immunomodulation; Protéine de S-Layer; Mucosite; Propionibacteria; Probiotic; Immunomodulation; S-Layer protein; Mucositis.

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APA (6^th Edition):

Rosa do carmo, F. L. (2018). La protéine de couche de surface SlpB assure la médiation de l’immunomodulation et de l’adhésion chez le probiotique Propionibacterium freudenreichii CIRM-BIA 129. : Surface layer protein SlpB mediates immunodulation and adhesion in the probiotic Propionibacterium freudenreichii CIRM-BIA 129. (Doctoral Dissertation). Rennes, Agrocampus Ouest; UNIVERSIDADEFEDERALDEMINASGERAIS, UFMG. Retrieved from http://www.theses.fr/2018NSARB315

Chicago Manual of Style (16^th Edition):

Rosa do carmo, Fillipe Luiz. “La protéine de couche de surface SlpB assure la médiation de l’immunomodulation et de l’adhésion chez le probiotique Propionibacterium freudenreichii CIRM-BIA 129. : Surface layer protein SlpB mediates immunodulation and adhesion in the probiotic Propionibacterium freudenreichii CIRM-BIA 129.” 2018. Doctoral Dissertation, Rennes, Agrocampus Ouest; UNIVERSIDADEFEDERALDEMINASGERAIS, UFMG. Accessed January 23, 2021. http://www.theses.fr/2018NSARB315.

MLA Handbook (7^th Edition):

Rosa do carmo, Fillipe Luiz. “La protéine de couche de surface SlpB assure la médiation de l’immunomodulation et de l’adhésion chez le probiotique Propionibacterium freudenreichii CIRM-BIA 129. : Surface layer protein SlpB mediates immunodulation and adhesion in the probiotic Propionibacterium freudenreichii CIRM-BIA 129.” 2018. Web. 23 Jan 2021.

Vancouver:

Rosa do carmo FL. La protéine de couche de surface SlpB assure la médiation de l’immunomodulation et de l’adhésion chez le probiotique Propionibacterium freudenreichii CIRM-BIA 129. : Surface layer protein SlpB mediates immunodulation and adhesion in the probiotic Propionibacterium freudenreichii CIRM-BIA 129. [Internet] [Doctoral dissertation]. Rennes, Agrocampus Ouest; UNIVERSIDADEFEDERALDEMINASGERAIS, UFMG; 2018. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2018NSARB315.

Council of Science Editors:

Rosa do carmo FL. La protéine de couche de surface SlpB assure la médiation de l’immunomodulation et de l’adhésion chez le probiotique Propionibacterium freudenreichii CIRM-BIA 129. : Surface layer protein SlpB mediates immunodulation and adhesion in the probiotic Propionibacterium freudenreichii CIRM-BIA 129. [Doctoral Dissertation]. Rennes, Agrocampus Ouest; UNIVERSIDADEFEDERALDEMINASGERAIS, UFMG; 2018. Available from: http://www.theses.fr/2018NSARB315

21. Fan, Ye. L'effet immunomodulateur de cellule souche mésenchymateuse et ses exosomes sur l'activité des lymphocytes : Regulation of Lymphocytes Activity by Mesenchymal Stem Cells and their Exosomes.

Degree: Docteur es, Sciences de la vie et de la santé, 2017, Université Paris-Saclay (ComUE)

URL: http://www.theses.fr/2017SACLS194

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Introduction : Les cellules souche mésenchymateuse (CSM) présentent une puissante activité immunomodulatrice sur les lymphocytes T et les Natural Killer (NK), impliquées dans les réactions… (more)

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Introduction : Les cellules souche mésenchymateuse (CSM) présentent une puissante activité immunomodulatrice sur les lymphocytes T et les Natural Killer (NK), impliquées dans les réactions allogéniques. Les propriétés immunomodulatrices des CSM dépendent de contacts cellulaires et des facteurs secrétés. Ainsi les exosomes produits par ces cellules pourraient constituer des nouveaux produits thérapeutiques.L’objectif de ce travail est d’étudier, in vitro, l’effet d’exosomes dérivés de CSM sur les lymphocytes B, T et les NK.Méthodologie : Les CSMs utilisées sont issues de foies fœtaux humains. Les exosomes ont été isolés à partir du milieu de culture des CSMs par une série d’ultracentrifugation à 100000g.Résultats : Contrairement aux CSMs qui inhibent la prolifération des lymphocytes T et B, leurs exosomes n'ont pas d'effet sur leur prolifération. Cependant ils inhibent la prolifération, l’activation et la cytotoxicité (expresion CD107a) des NK. Nous avons mit en évidence, par FACS, la présence de TGFbeta; à la surface des exosomes. De plus leur fonction inhibitrice est abrogé en présence d’un anticorps bloquants anti-TGFbeta;. Réciproquement l’exposition de cellules NK à du TGFbeta; inhibe la cytotoxicité et la prolifération de cellules. Enfin, en présence d'exososmes nous avons montré, par IF, une translocation de Smad 2/3 (messager du signal TGFbeta;) dans les noyaux des cellules NK, inhibé par l'ajout d'anticorps anti-TGFbeta;.Conclusion: Ces résultats suggère que les propriétés immunomodulatrices de CSMs sur NK pourraient dépendre de TGFβ présenté ou associé aux exosomes.

Introduction: Mesenchymal stem cells (MSCs) are powerful immunomodulators regulating the function of B and T lymphocytes and natural killers cells (NK) involved in allogeneic reactions. Their immunomodulatory properties depend on cell contact and secretion factors produced by MSCs. Thus exosomes produced by these cells could provide new therapeutic tools.Objective: The objective of this work is to study the effect of MSC derived exosomes in vitro on B and T lymphocytes and NK cells.Method: MSCs used for this study are isolated from human fetal liver. Exosomes were isolated from MSC culture medium by a serie of ultracentrifugation at 100000g.Results: MSCs inhibit the proliferation of T lymphocytes. Unlike MSCs, their exosomes do not abrogate the proliferation of T and B cells. However they inhibit the proliferation, activation and cytotoxicity (CD107a expression) of NK cells. By FACS analysis we showed a surface expression of TGFb; by exosomes. Inhibition of NK cells activation by exosomes is altered by a neutralizing anti-TGFb; antibody. Contrary when NK cells are cultured with TGFb; the same effect qs exosomes is demonstrated. By IF, we found a nuclear translocation of Smad 2/3 (TGFb; signal transducer) in NK cells cultured with exosomes, which is inhibited by the qddition of anti-TGFb; antibody.Conclusion: These results suggest that the immunomodulatory properties of MSCs on NK could depend on exosome presentation or association with TGFb;.

Advisors/Committee Members: Dürrbach, Antoine (thesis director).

Subjects/Keywords: Cellules souches mésenchymateuses; Exosomes; Immunomodulation; Cellules NK; Mesenchymal stem cells; Exosomes; Immunomodulation; NK cells

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fan, Y. (2017). L'effet immunomodulateur de cellule souche mésenchymateuse et ses exosomes sur l'activité des lymphocytes : Regulation of Lymphocytes Activity by Mesenchymal Stem Cells and their Exosomes. (Doctoral Dissertation). Université Paris-Saclay (ComUE). Retrieved from http://www.theses.fr/2017SACLS194

Chicago Manual of Style (16^th Edition):

Fan, Ye. “L'effet immunomodulateur de cellule souche mésenchymateuse et ses exosomes sur l'activité des lymphocytes : Regulation of Lymphocytes Activity by Mesenchymal Stem Cells and their Exosomes.” 2017. Doctoral Dissertation, Université Paris-Saclay (ComUE). Accessed January 23, 2021. http://www.theses.fr/2017SACLS194.

MLA Handbook (7^th Edition):

Fan, Ye. “L'effet immunomodulateur de cellule souche mésenchymateuse et ses exosomes sur l'activité des lymphocytes : Regulation of Lymphocytes Activity by Mesenchymal Stem Cells and their Exosomes.” 2017. Web. 23 Jan 2021.

Vancouver:

Fan Y. L'effet immunomodulateur de cellule souche mésenchymateuse et ses exosomes sur l'activité des lymphocytes : Regulation of Lymphocytes Activity by Mesenchymal Stem Cells and their Exosomes. [Internet] [Doctoral dissertation]. Université Paris-Saclay (ComUE); 2017. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2017SACLS194.

Council of Science Editors:

Fan Y. L'effet immunomodulateur de cellule souche mésenchymateuse et ses exosomes sur l'activité des lymphocytes : Regulation of Lymphocytes Activity by Mesenchymal Stem Cells and their Exosomes. [Doctoral Dissertation]. Université Paris-Saclay (ComUE); 2017. Available from: http://www.theses.fr/2017SACLS194

22. Kazma, Ihab. Modulation de l'alloréactivité et des fonctions des cellules dendritiques humaines par différentes populations de lymphocytes T préactivés : Modulation of alloreactivity and functions of Human dendritic cells by different preactivated T cell populations.

Degree: Docteur es, Sciences de la Vie et de la Santé, 2014, Université François-Rabelais de Tours

URL: http://www.theses.fr/2014TOUR3301

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Notre équipe a démontré précédemment que les cellules dendritiques (DC) traitées par l’Acide Mycophénolique (DC-MPA) induisaient des lymphocytes T (LT) CD4+ régulateurs (iTreg). Dans ce… (more)

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Notre équipe a démontré précédemment que les cellules dendritiques (DC) traitées par l’Acide Mycophénolique (DC-MPA) induisaient des lymphocytes T (LT) CD4+ régulateurs (iTreg). Dans ce travail, nous avons démontré que les iTreg supprimaient l’allocytotoxicité des LT CD8+ indépendants des LT CD4+. D’autre part, nous avons montré que des LT préactivés en conditions inflammatoires induisaient via CTLA-4 la synthèse d’IL-12 par les DC. Le blocage de CD28 dans les mêmes conditions inhibait la production d’IL-10 et d’Interferon-g mais n’affectait pas celle d’IL-12. Enfin, des LT préactivés par des DC allogéniques différenciées en présence d’IL-10 (DC-10) étaient hyporéactifs, mais de façon surprenante, étaient dénués d’activité régulatrice. Ce travail a montré pour la première fois chez l’homme la capacité des Treg induits à réguler l’allocytotoxicité des LT CD8+. Il suggère aussi que CTLA-4 exprimée par des LT préactivés orientait la réponse immunitaire vers Th1, via un ligand sur la DC, non commun avec CD28.

This work has studied several aspects of the regulation of the immune response in human. Works in our laboratory have previously demonstrated that Mycophenolic Acid-Treated Dendritic Cells (MPA-DC) induced CD4+ regulatory T cells (iTreg). In this work and for the first time in human, we demonstrated that allospecific iTreg suppressed helpless CD8+ T-Cells allocytotoxicity. On the other hand, we have shown that preactivated T-Cells in inflammatory conditions induce IL-12 synthesis by DC through CTLA-4 engagement. Blockade of CD28 in this interaction inhibited the production of IL-10 and Interferon-g without affecting that of IL-12. Finally, allogeneic DC differentiated in the presence of IL-10 (DC-10) induced T cell hyporesponsiveness without any regulatory activity. This work has highlighted the ability of allospecific iTreg to regulate CD8+ T-Cells allocytotoxicity and suggested that the engagement of CTLA-4 expressed by preactivated T cells polarized the immune response towards Th1, via a ligand on DC, different from that of CD28.

Advisors/Committee Members: Baron, Christophe (thesis director).

Subjects/Keywords: Cellules dendritiques; Lymphocytes T régulateurs; Cytotoxicité; Immunomodulation; Dendritic cells; Regulatory T cells; Cytotoxicity; Immunomodulation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kazma, I. (2014). Modulation de l'alloréactivité et des fonctions des cellules dendritiques humaines par différentes populations de lymphocytes T préactivés : Modulation of alloreactivity and functions of Human dendritic cells by different preactivated T cell populations. (Doctoral Dissertation). Université François-Rabelais de Tours. Retrieved from http://www.theses.fr/2014TOUR3301

Chicago Manual of Style (16^th Edition):

Kazma, Ihab. “Modulation de l'alloréactivité et des fonctions des cellules dendritiques humaines par différentes populations de lymphocytes T préactivés : Modulation of alloreactivity and functions of Human dendritic cells by different preactivated T cell populations.” 2014. Doctoral Dissertation, Université François-Rabelais de Tours. Accessed January 23, 2021. http://www.theses.fr/2014TOUR3301.

MLA Handbook (7^th Edition):

Kazma, Ihab. “Modulation de l'alloréactivité et des fonctions des cellules dendritiques humaines par différentes populations de lymphocytes T préactivés : Modulation of alloreactivity and functions of Human dendritic cells by different preactivated T cell populations.” 2014. Web. 23 Jan 2021.

Vancouver:

Kazma I. Modulation de l'alloréactivité et des fonctions des cellules dendritiques humaines par différentes populations de lymphocytes T préactivés : Modulation of alloreactivity and functions of Human dendritic cells by different preactivated T cell populations. [Internet] [Doctoral dissertation]. Université François-Rabelais de Tours; 2014. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2014TOUR3301.

Council of Science Editors:

Kazma I. Modulation de l'alloréactivité et des fonctions des cellules dendritiques humaines par différentes populations de lymphocytes T préactivés : Modulation of alloreactivity and functions of Human dendritic cells by different preactivated T cell populations. [Doctoral Dissertation]. Université François-Rabelais de Tours; 2014. Available from: http://www.theses.fr/2014TOUR3301

23. Villeger, Romain. Etude in vitro des propriétés probiotiques de bactéries du genre Bacillus : Interaction avec l’hôte et effets de l’association avec un prébiotique : In vitro study of probiotic Bacillus strains : interaction with the host and effect of association with a prébiotic.

Degree: Docteur es, Biochimie et microbiologie appliquée, 2014, Limoges

URL: http://www.theses.fr/2014LIMO0066

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Les probiotiques sont des microorganismes vivants qui, lorsqu’ils sont ingérés en quantité adéquate, peuvent exercer des propriétés bénéfiques sur la santé de l’hôte. Les souches… (more)

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Les probiotiques sont des microorganismes vivants qui, lorsqu’ils sont ingérés en quantité adéquate, peuvent exercer des propriétés bénéfiques sur la santé de l’hôte. Les souches de Bacillus utilisées en tant que probiotiques ne sont pas colonisatrices du tractus intestinal, mais sont des résidents transitoires du microbiote. Ce travail fait l’investigation in vitro de l’association, qualifiée de synbiotique, entre une souche probiotique de Bacillus subtilis et une source carbonée prébiotique, composé alimentaire peu digéré par les enzymes intestinales mais utilisable par les bactéries dans l’intestin. L’étude de cette association met en évidence la capacité de la souche à utiliser les isomaltooligosaccharides (IMOS) prébiotiques comme unique substrat carboné. L’effet positif de ce substrat sur la tolérance à la bile de la souche a été démontré in vitro. Les résultats d’une analyse protéomique faisant l’étude des enzymes clés impliquées dans le métabolisme des IMOS, ainsi que d’autres biomarqueurs d’intérêt probiotique, sont en cours d’exploitation. Ce travail préliminaire d’investigation de l’association synbiotique entre les IMOS prébiotiques et la souche probiotique B. subtilis, aboutira à des essais in vivo. Les effets bénéfiques des probiotiques du genre Bacillus, notamment au niveau de la modulation du système immunitaire, résultent de l’interaction entre les molécules de la surface bactérienne et les cellules de l’intestin. Les mécanismes moléculaires à l’origine de l’immunomodulation sont mal connus, alors que leur compréhension est nécessaire à l’optimisation de l’utilisation du probiotique. Un deuxième volet de ce travail concerne la comparaison des structures d’entités moléculaires de surface de trois Bacilli probiotiques, les acides lipotéichoïques (LTAs), et leurs activités immunologiques respectives. Une étude structurale des LTAs par des méthodes biochimiques et par RMN a permis de mettre en évidence la diversité structurale au sein du même genre Bacillus. Le rôle clé de la D-alanine dans l’activité biologique de ces antigènes bactériens a été démontré.

Probiotics are live microorganisms, which when administered in adequate amounts confer a health benefit on the host. Bacillus probiotic strains are not able to colonize the gut, and are considered as transient residents of the microbiota. Prebiotic are non-digestible food ingredients that could stimulate growth of bacteria in the gut. This work investigates the in vitro effect of a prebiotic isomaltooligosaccharide (IMOS) on the growth of a probiotic strain Bacillus subtilis. This study highlights the ability of the strain to use IMOS as unique carbon source. A comparative proteomic analysis investigates the main enzymes implicated in the prebiotic metabolism, and biomarkers possibly involved in probiotic effects. This preliminary work, which studies the synbiotic association between a probiotic and a prebiotic, will lead to in vivo assays. Beneficial effects of probiotic Bacilli, mainly modulation of intestinal immune system, result from interaction…

Advisors/Committee Members: Bressollier, Philippe (thesis director), Ouk, Tan-Sothéa (thesis director).

Subjects/Keywords: Bacillus probiotique; Prébiotique; Synbiotique; Tolérance à la bile; Immunomodulation; Acides lipotéichoïques; Probiotic Bacillus; Prebiotic; Synbiotic; Bile tolerance; Immunomodulation; Lipoteichoic acids; 613.28

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Villeger, R. (2014). Etude in vitro des propriétés probiotiques de bactéries du genre Bacillus : Interaction avec l’hôte et effets de l’association avec un prébiotique : In vitro study of probiotic Bacillus strains : interaction with the host and effect of association with a prébiotic. (Doctoral Dissertation). Limoges. Retrieved from http://www.theses.fr/2014LIMO0066

Chicago Manual of Style (16^th Edition):

Villeger, Romain. “Etude in vitro des propriétés probiotiques de bactéries du genre Bacillus : Interaction avec l’hôte et effets de l’association avec un prébiotique : In vitro study of probiotic Bacillus strains : interaction with the host and effect of association with a prébiotic.” 2014. Doctoral Dissertation, Limoges. Accessed January 23, 2021. http://www.theses.fr/2014LIMO0066.

MLA Handbook (7^th Edition):

Villeger, Romain. “Etude in vitro des propriétés probiotiques de bactéries du genre Bacillus : Interaction avec l’hôte et effets de l’association avec un prébiotique : In vitro study of probiotic Bacillus strains : interaction with the host and effect of association with a prébiotic.” 2014. Web. 23 Jan 2021.

Vancouver:

Villeger R. Etude in vitro des propriétés probiotiques de bactéries du genre Bacillus : Interaction avec l’hôte et effets de l’association avec un prébiotique : In vitro study of probiotic Bacillus strains : interaction with the host and effect of association with a prébiotic. [Internet] [Doctoral dissertation]. Limoges; 2014. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2014LIMO0066.

Council of Science Editors:

Villeger R. Etude in vitro des propriétés probiotiques de bactéries du genre Bacillus : Interaction avec l’hôte et effets de l’association avec un prébiotique : In vitro study of probiotic Bacillus strains : interaction with the host and effect of association with a prébiotic. [Doctoral Dissertation]. Limoges; 2014. Available from: http://www.theses.fr/2014LIMO0066

24. Letscher, Hélène. Étude des propriétés régulatrices d’une population de précurseurs de cellules dendritiques plasmacytoïdes conditionnée par le CpG dans le cadre de réponses auto-immune et allogénique : Study of a population of suppressor hematopoietic precursor cells in autoimmune and allogeneic response.

Degree: Docteur es, Immunologie, 2018, Sorbonne Paris Cité

URL: http://www.theses.fr/2018USPCB058

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Les progéniteurs hématopoïétiques présentent la faculté de détecter des signaux infectieux et inflammatoires. Leur éducation précoce par de tels signaux au sein de la moelle… (more)

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Les progéniteurs hématopoïétiques présentent la faculté de détecter des signaux infectieux et inflammatoires. Leur éducation précoce par de tels signaux au sein de la moelle osseuse avant leur sortie vers la périphérie peut influencer l'évolution des réponses immunes. Alors que les cellules dendritiques plasmacytoïdes matures peuvent soit aggraver soit améliorer des maladies auto-immunes ou allogéniques, nous avons exploré la possibilité que de tels signaux innés confèrent des propriétés immunorégulatrices à des précurseurs médullaires des pDC. Nous avons caractérisé une population médullaire émergeant après interaction avec un agoniste du Toll-like receptor-9, l'oligonucléotide CpG, qui présente le phénotype c-kit+Sca-1+B220intPDCA-1+, est engagée dans la voie des cellules dendritiques plasmacytoïdes (pDC) et l'avons dénommée CpG-pre-pDC. Nous avons évalué le potentiel immunorégulateur des CpG-prepDCs en opérant leur transfert adoptif dans deux types de pathologies murines : l'Encéphalite Auto-immune Expérimentales (EAE), un modèle de sclérose en plaques qui est une maladie auto-immune, ainsi que la maladie du greffon contre l'hôte (GVHD) qui est une réponse allogénique. Il s'est avéré que le transfert d'un nombre assez faible de précurseurs (80 000 en EAE et 200 000 en GVHD) est capable de limiter la maladie à différents temps cliniques. De façon intéressante, les CpG-pre-pDC migrent spécifiquement à la moelle épinière dans l'EAE et à la rate dans la GVHD où leur descendance conserve un phénotype de pDC encore relativement immature. Dans le cadre de l'EAE, la descendance des précurseurs injectés produit essentiellement de l'IL-27 et du TGFß et plus modestement du GM-CSF. Au niveau du système nerveux central inflammé, elles font dévier la réponse immunitaire des lymphocytes T CD4+ infiltrants d'un profil pro-inflammatoire (IFNy+ GM-CSF+ IL-17+) vers un profil anti-inflammatoire (TGFß+, IL-27+, IL-17-, GM-CSFlo). L'utilisation de précurseurs déficients dans chacune de ces deux cytokines a permis de démontrer que TGFß et IL-27 interviennent séquentiellement dans la protection conférée par les CpG-prepDCs, le TGFß à des temps précoces et l'IL-27 aux phases tardives de la maladie. Des mécanismes semblables interviennent dans la protection envers la GVHD conférée par les CpG-prepDCs, car leur descendance est toujours capable de produire du TGFß mais cette fois en association avec l'IL-12, une autre cytokine de la même famille que l'IL-27. Par ailleurs, ces cellules sont capables de diminuer la production d'IL-17 tant par les lymphocytes T CD4+ que par les CD8+. Une thérapie cellulaire avec l'équivalent humain des CpG-pre-pDCs pourrait constituer un nouvel outil thérapeutique pour le traitement à la fois de la sclérose en plaques réfractaire et de la maladie du greffon contre l'hôte soit injectés seuls soit en enrichissement des greffes de cellules souches hématopoïétiques qui sont pratiquées dans ces deux maladies.

Hematopoietic progenitors can sense innate signals. Their early education by such signals within the…

Advisors/Committee Members: Zavala, Flora (thesis director).

Subjects/Keywords: Précurseurs hématopoïetiques; Cellules dendritiques plasmacytoïdes; Immunomodulation; GVHD; EAE; Hematopoietic precursors; Plasmacytoid dendritic cells; Immunomodulation; GVHD; EAE; 616.07

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Letscher, H. (2018). Étude des propriétés régulatrices d’une population de précurseurs de cellules dendritiques plasmacytoïdes conditionnée par le CpG dans le cadre de réponses auto-immune et allogénique : Study of a population of suppressor hematopoietic precursor cells in autoimmune and allogeneic response. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2018USPCB058

Chicago Manual of Style (16^th Edition):

Letscher, Hélène. “Étude des propriétés régulatrices d’une population de précurseurs de cellules dendritiques plasmacytoïdes conditionnée par le CpG dans le cadre de réponses auto-immune et allogénique : Study of a population of suppressor hematopoietic precursor cells in autoimmune and allogeneic response.” 2018. Doctoral Dissertation, Sorbonne Paris Cité. Accessed January 23, 2021. http://www.theses.fr/2018USPCB058.

MLA Handbook (7^th Edition):

Letscher, Hélène. “Étude des propriétés régulatrices d’une population de précurseurs de cellules dendritiques plasmacytoïdes conditionnée par le CpG dans le cadre de réponses auto-immune et allogénique : Study of a population of suppressor hematopoietic precursor cells in autoimmune and allogeneic response.” 2018. Web. 23 Jan 2021.

Vancouver:

Letscher H. Étude des propriétés régulatrices d’une population de précurseurs de cellules dendritiques plasmacytoïdes conditionnée par le CpG dans le cadre de réponses auto-immune et allogénique : Study of a population of suppressor hematopoietic precursor cells in autoimmune and allogeneic response. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2018. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2018USPCB058.

Council of Science Editors:

Letscher H. Étude des propriétés régulatrices d’une population de précurseurs de cellules dendritiques plasmacytoïdes conditionnée par le CpG dans le cadre de réponses auto-immune et allogénique : Study of a population of suppressor hematopoietic precursor cells in autoimmune and allogeneic response. [Doctoral Dissertation]. Sorbonne Paris Cité; 2018. Available from: http://www.theses.fr/2018USPCB058

25. Martirosyan, Anna. Le dévelopement et la modulation des réponses immunes par la bactérie intracellulaire Brucella : The induction and modulation of immune responses by the intracellular pathogen Brucella spp.

Degree: Docteur es, Immunologie, 2012, Aix Marseille Université

URL: http://www.theses.fr/2012AIXM4042

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Les différents agents pathogènes ont développé de multiples stratégies pour contourner ou modifier les mécanismes de défense de l'hôte. La bactérie intracellulaire Brucella n'est pas… (more)

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Les différents agents pathogènes ont développé de multiples stratégies pour contourner ou modifier les mécanismes de défense de l'hôte. La bactérie intracellulaire Brucella n'est pas une exception à la règle, car elle a développé des mécanismes qui lui permettent d'échapper à la surveillance immunitaire, persister pendant de longues périodes dans l'hôte et établir une infection chronique. En effet, Brucella responsable de la brucellose ou fièvre de Malte. La brucellose est une zoonose en réémergence ; dans cette maladie l'homme infecté représente une impasse épidémiologique. Il est indispensable de mieux connaître l'immunité développée contre Brucella qui est un excellent modèle d'étude d'autres maladies chroniques bactériennes. Le projet de thèse a été centré sur le développement et la modulation des réponses immunes par Brucella et les molécules bactériennes. Dans la première partie de cette thèse, nous avons analysé les réponses immunitaires innées et adaptatives lors de l'infection avec Brucella. D'une part, nous avons étudié l'influence des neutrophiles dans la réponse immunitaire lors de l'infection, en étudiant le cours de brucellose dans les modèles de souris neutropéniques. D'autre part, nous avons identifié et caractérisé in vivo une population des cellules CD4+ cytotoxiques au cours des infections avec Brucella. Dans la deuxième partie, nous nous sommes intéressés dans les modèles murins et humains aux propriétés immunomodulatrices des différentes molécules bactériennes telles que les glucans cycliques et des lipopolysaccharides (LPS).

Various successful pathogens have evolved multiple mechanisms to overcome or alter many normally very effective host defense mechanisms, including both innate and acquired immunity. The intracellular pathogen Brucella is not an exception to the rule as it displays mechanisms that allow it to evade immune surveillance and that are required to establish persistent infections in mammals. In this work, we studied the induction and modulation of immune responses by the intracellular bacteria Brucella and bacterial components. In the first part of this thesis, we have performed a systemic analysis of the innate and adaptive immune responses upon Brucella infection. On the one hand, we investigated the influence of polymorphonuclear neutrophils (PMNs) in the immune response during Brucella infection by exploring the course of brucellosis in antibody neutropenic mouse models. On the other hand, we identified and characterized in vivo a cytotoxic CD4+ T cell population upon Brucella abortus and Salmonella thyphimurium infections. In the second part, we focused on the immunomodulatory properties of various bacterial components such as cyclic glucans and lipopolysaccharides (LPS) both in mouse and human models.

Advisors/Committee Members: Gorvel, Jean-Pierre (thesis director).

Subjects/Keywords: Bactérie intracellulaire; Immunomodulation; Molécules bactériennes; Réponses immunitaires innées et adaptatives; Intracellular bacteria; Immunomodulation, bacterial molecules; Innate and adaptive immune responses

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Martirosyan, A. (2012). Le dévelopement et la modulation des réponses immunes par la bactérie intracellulaire Brucella : The induction and modulation of immune responses by the intracellular pathogen Brucella spp. (Doctoral Dissertation). Aix Marseille Université. Retrieved from http://www.theses.fr/2012AIXM4042

Chicago Manual of Style (16^th Edition):

Martirosyan, Anna. “Le dévelopement et la modulation des réponses immunes par la bactérie intracellulaire Brucella : The induction and modulation of immune responses by the intracellular pathogen Brucella spp.” 2012. Doctoral Dissertation, Aix Marseille Université. Accessed January 23, 2021. http://www.theses.fr/2012AIXM4042.

MLA Handbook (7^th Edition):

Martirosyan, Anna. “Le dévelopement et la modulation des réponses immunes par la bactérie intracellulaire Brucella : The induction and modulation of immune responses by the intracellular pathogen Brucella spp.” 2012. Web. 23 Jan 2021.

Vancouver:

Martirosyan A. Le dévelopement et la modulation des réponses immunes par la bactérie intracellulaire Brucella : The induction and modulation of immune responses by the intracellular pathogen Brucella spp. [Internet] [Doctoral dissertation]. Aix Marseille Université 2012. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2012AIXM4042.

Council of Science Editors:

Martirosyan A. Le dévelopement et la modulation des réponses immunes par la bactérie intracellulaire Brucella : The induction and modulation of immune responses by the intracellular pathogen Brucella spp. [Doctoral Dissertation]. Aix Marseille Université 2012. Available from: http://www.theses.fr/2012AIXM4042

26. Kökten, Tunay. L'innervation en ingénierie dentaire : The innervation in tooth engineering.

Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2014, Université de Strasbourg

URL: http://www.theses.fr/2014STRAJ073

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Notre approche biomimétique permet de régénérer une dent entière. Un protocole en deux étapes à partir de réassociations de cellules dentaires embryonnaires permet le développement… (more)

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Notre approche biomimétique permet de régénérer une dent entière. Un protocole en deux étapes à partir de réassociations de cellules dentaires embryonnaires permet le développement de la couronne in vitro et, après implantation, la différenciation fonctionnelle des cellules, l’initiation du développement radiculaire et la vascularisation dentaire. Cependant, l’absence d’innervation a nécessité des expériences complémentaires :- La co-implantation de réassociations cellulaires avec un ganglion trigéminal permet la croissance d’axones autour de la dent formée, mais pas dans le mésenchyme dentaire.- Pour tenter de résoudre ce problème, la régénération axonale a été testée dans un contexte immunodéprimé en utilisant la cyclosporine A (CsA). Dans ces conditions, des fibres nerveuses entrent dans la pulpe dentaire, jusqu’aux odontoblastes. Cependant, la CsA a aussi un effet direct sur la croissance axonale.- Des co-implantations chez des souris immunodéprimées (Nude) montrent que l’immunomodulation seule suffit pour l’innervation de la dent.- Dans la dent, les axones assurent différentes fonctions en interagissant avec les cellules voisines. Les relations entre axones et autres cellules (odontoblastes, cellules endothéliales, péricytes et cellules gliales) ont été analysées dans les mésenchymes dentaire et péri-dentaire de réassociations implantées et comparées à ce que l’on observe pour une molaire physiologique à un stade similaire.Ce travail décrit les conditions permettant l’innervation des dents régénérées. Des expériences préliminaires encourageantes ont été réalisées avec des cellules souches pour remplacer la CsA.

Our biomimetic approach allowed the regeneration of a whole tooth. Using embryonic dental cells, a two-steps protocol allowed crown formation in vitro and, after implantation, functional cells differentiation, initiation of root formation and tooth vascularization. However, the teeth were not innervated, which led to complementary experiments:- The co-implantation of cell re-associations with a trigeminal ganglion allowed axonal growth around the forming teeth, but not in the dental mesenchyme. - To try to solve this point, axonal regeneration was tested in immunodepressed conditions, using cyclosporin A (CsA). In these conditions, nerve fibers entered the dental pulp and reached odontoblasts. However, CsA shows multiple effects, including direct ones on nerve growth. - Co-implantations were performed in immunocompromised Nude mice allowed axons to reach the odontoblast layer, thus showing that immunomodulation is sufficient.- Axons in the dental mesenchyme interfere with several functions by interacting with neighbor cells. Relationships between axons and other cells (odontoblasts, endothelial cells, pericytes and glial cells) were analyzed in the peridental and dental mesenchymes of implanted reassociations and compared to the physiological situation in developing molars at similar stage. This work describes conditions allowing the innervation of engineered teeth. Preliminary encouraging attempts…

Advisors/Committee Members: Lesot, Hervé (thesis director).

Subjects/Keywords: Ingénierie de l’organe dentaire; Innervation; Vascularisation; Cellules gliales; Immunomodulation; Souris; Tooth organ engineering; Innervation; Vascularization; Glial cells; Immunomodulation; Mouse; 571.5; 617.6

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kökten, T. (2014). L'innervation en ingénierie dentaire : The innervation in tooth engineering. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2014STRAJ073

Chicago Manual of Style (16^th Edition):

Kökten, Tunay. “L'innervation en ingénierie dentaire : The innervation in tooth engineering.” 2014. Doctoral Dissertation, Université de Strasbourg. Accessed January 23, 2021. http://www.theses.fr/2014STRAJ073.

MLA Handbook (7^th Edition):

Kökten, Tunay. “L'innervation en ingénierie dentaire : The innervation in tooth engineering.” 2014. Web. 23 Jan 2021.

Vancouver:

Kökten T. L'innervation en ingénierie dentaire : The innervation in tooth engineering. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2014. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2014STRAJ073.

Council of Science Editors:

Kökten T. L'innervation en ingénierie dentaire : The innervation in tooth engineering. [Doctoral Dissertation]. Université de Strasbourg; 2014. Available from: http://www.theses.fr/2014STRAJ073

27. Wehbe, Batoul. IgA et rein : destructrice ou protectrice ? : Rôles de l'immunoglobuline A (IgA) dans deux pathologies rénales : IgA and kidney : Role of immunoglobulin A (IgA) on two renal pathologies.

Degree: Docteur es, Immunologie, oncologie et infectiologie, 2018, Limoges; Université libanaise

URL: http://www.theses.fr/2018LIMO0034

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L’immunoglobuline A (IgA) est l’immunoglobuline la plus abondamment synthétisée chez les mammifères. Ses propriétés ambivalentes l’impliquent non seulement dans des fonctions de protection contre les… (more)

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L’immunoglobuline A (IgA) est l’immunoglobuline la plus abondamment synthétisée chez les mammifères. Ses propriétés ambivalentes l’impliquent non seulement dans des fonctions de protection contre les agents pathogènes mais aussi dans des phénomènes de tolérance immunitaire vis-à-vis des germes commensaux du microbiote. Toutefois, les IgA peuvent développer des propriétés pathogènes. Dans la première partie de mon travail de thèse, nous avons étudié les effets pathogènes de l’IgA. Les dépôts d’IgA sur le mésangium sont la caractéristique de l’IgAN. La physiopathologie de cette maladie est mal connue. L’hypothèse d’un défaut de glycosylation de l’IgA est souvent retenue ; ce défaut peut être la cause de sa polymérisation et de son antigénicité, il peut aussi favoriser le clivage du récepteur CD89. Nous avons analysé l’effet du défaut d’affinité de la région variable des IgA, de la substitution de la chaîne légère ainsi que de l’association des IgA à leur récepteur, le CD89 sur l’induction des lésions et le dysfonctionnement rénal chez quatre modèles murins différents générés au laboratoire et suivis pendant 12 mois. Nous avons également étudié les propriétés physico-chimiques des IgA de 28 patients ayant une dysglobulinémie et de 28 IgA produites par des hybridomes ; la relation entre ces propriétés et la capacité des IgA à se déposer a été observée. Dans une seconde partie, nous avons étudié l’aspect immunomodulateur et les propriétés antiinflammatoires conférées par l’IgA humaine surexprimée chez un modèle murin de lupus systémique (souris MRL/lpr). Dans la dernière partie du travail, nous avons contribué à la caractérisation d’un modèle de souris transgénique exprimant l’IgA de classe 2 et à l’étude de l’effet de signalisation médiée par cette IgA2 sur le développement des populations lymphocytaires. L’ensemble de ces travaux a montré l’effet pathogène des IgA naturelles ayant une faible affinité sur le développement de la néphropathie à IgA ; ainsi les analyses des IgA des patients et des hybridomes montrent que c’est la stabilité moléculaire de préférence au profil de glycosylation qui joue un rôle crucial dans leur capacité de dépôt. L’expression des IgA humaines chez les souris lupiques a considérablement prolongé leur durée de vie et a ralenti la survenue de l’auto-immunité et de l’atteinte rénale ce qui témoigne du rôle anti-inflammatoire des IgA. L’étude du modèle murin exprimant l’IgA2 humaine a montré que la signalisation via l’IgA2 joue un rôle inhibiteur sur le développement précoce de certaines sous-populations de cellules B. L’ensemble de ces résultats montrent la multitude d’effets de l’IgA lui permettant d’intervenir d’une part dans la pathogenèse d’une maladie complexe (l’IgAN) et d’autre part dans la protection de l’auto-immunité, témoignant de la complexité des interactions mises en jeu et du caractère régulateur de cette immunoglobuline.

Immunoglobulin A (IgA) is the most synthetized immunoglobulin in mammals. IgA has ambivalent properties: it is implicated in the mechanisms of defense against…

Advisors/Committee Members: Aldigier, Jean-Claude (thesis director), Badran, Bassam (thesis director), Cogné, Michel (thesis director), El Makhour, Yolla (thesis director).

Subjects/Keywords: Immunoglobuline A; Modèle murin; Néphropathie à IgA; Immunomodulation; IgA2; Immunoglobulin A; Mouse model; IgA nephropathy; Immunomodulation; IgA2; 615.37

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wehbe, B. (2018). IgA et rein : destructrice ou protectrice ? : Rôles de l'immunoglobuline A (IgA) dans deux pathologies rénales : IgA and kidney : Role of immunoglobulin A (IgA) on two renal pathologies. (Doctoral Dissertation). Limoges; Université libanaise. Retrieved from http://www.theses.fr/2018LIMO0034

Chicago Manual of Style (16^th Edition):

Wehbe, Batoul. “IgA et rein : destructrice ou protectrice ? : Rôles de l'immunoglobuline A (IgA) dans deux pathologies rénales : IgA and kidney : Role of immunoglobulin A (IgA) on two renal pathologies.” 2018. Doctoral Dissertation, Limoges; Université libanaise. Accessed January 23, 2021. http://www.theses.fr/2018LIMO0034.

MLA Handbook (7^th Edition):

Wehbe, Batoul. “IgA et rein : destructrice ou protectrice ? : Rôles de l'immunoglobuline A (IgA) dans deux pathologies rénales : IgA and kidney : Role of immunoglobulin A (IgA) on two renal pathologies.” 2018. Web. 23 Jan 2021.

Vancouver:

Wehbe B. IgA et rein : destructrice ou protectrice ? : Rôles de l'immunoglobuline A (IgA) dans deux pathologies rénales : IgA and kidney : Role of immunoglobulin A (IgA) on two renal pathologies. [Internet] [Doctoral dissertation]. Limoges; Université libanaise; 2018. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2018LIMO0034.

Council of Science Editors:

Wehbe B. IgA et rein : destructrice ou protectrice ? : Rôles de l'immunoglobuline A (IgA) dans deux pathologies rénales : IgA and kidney : Role of immunoglobulin A (IgA) on two renal pathologies. [Doctoral Dissertation]. Limoges; Université libanaise; 2018. Available from: http://www.theses.fr/2018LIMO0034

28. Chadet, Stéphanie. Rôle du récepteur purinergique P2Y11 dans la modulation du phénotype des cellules dendritiques et la survie des cardiomyocytes en situation d'hypoxie/réoxygénation : The role of P2Y11 receptor in the modulation of dendritic cell phenotype and cardiomyocyte survival during hypoxia/reoxygenation.

Degree: Docteur es, Sciences de la Vie et de la Santé, 2015, Université François-Rabelais de Tours

URL: http://www.theses.fr/2015TOUR3306

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Les cellules dendritiques (DCs) possèdent des rôles clés dans la modulation de la réponse inflammatoire. Leur implication dans la réponse inflammatoire post-ischémie/reperfusion semble claire. Cependant,… (more)

Subjects/Keywords: Cellule dendritique; Cardiomyocyte; Récepteur P2Y11; Immunomodulation; Signaux de danger; Dendritic cell; Cardiomyocyte; P2Y11 receptor; Immunomodulation; Danger signal

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chadet, S. (2015). Rôle du récepteur purinergique P2Y11 dans la modulation du phénotype des cellules dendritiques et la survie des cardiomyocytes en situation d'hypoxie/réoxygénation : The role of P2Y11 receptor in the modulation of dendritic cell phenotype and cardiomyocyte survival during hypoxia/reoxygenation. (Doctoral Dissertation). Université François-Rabelais de Tours. Retrieved from http://www.theses.fr/2015TOUR3306

Chicago Manual of Style (16^th Edition):

Chadet, Stéphanie. “Rôle du récepteur purinergique P2Y11 dans la modulation du phénotype des cellules dendritiques et la survie des cardiomyocytes en situation d'hypoxie/réoxygénation : The role of P2Y11 receptor in the modulation of dendritic cell phenotype and cardiomyocyte survival during hypoxia/reoxygenation.” 2015. Doctoral Dissertation, Université François-Rabelais de Tours. Accessed January 23, 2021. http://www.theses.fr/2015TOUR3306.

MLA Handbook (7^th Edition):

Chadet, Stéphanie. “Rôle du récepteur purinergique P2Y11 dans la modulation du phénotype des cellules dendritiques et la survie des cardiomyocytes en situation d'hypoxie/réoxygénation : The role of P2Y11 receptor in the modulation of dendritic cell phenotype and cardiomyocyte survival during hypoxia/reoxygenation.” 2015. Web. 23 Jan 2021.

Vancouver:

Chadet S. Rôle du récepteur purinergique P2Y11 dans la modulation du phénotype des cellules dendritiques et la survie des cardiomyocytes en situation d'hypoxie/réoxygénation : The role of P2Y11 receptor in the modulation of dendritic cell phenotype and cardiomyocyte survival during hypoxia/reoxygenation. [Internet] [Doctoral dissertation]. Université François-Rabelais de Tours; 2015. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2015TOUR3306.

Council of Science Editors:

Chadet S. Rôle du récepteur purinergique P2Y11 dans la modulation du phénotype des cellules dendritiques et la survie des cardiomyocytes en situation d'hypoxie/réoxygénation : The role of P2Y11 receptor in the modulation of dendritic cell phenotype and cardiomyocyte survival during hypoxia/reoxygenation. [Doctoral Dissertation]. Université François-Rabelais de Tours; 2015. Available from: http://www.theses.fr/2015TOUR3306

29. Benoist, Lauriane. Rôle du récepteur purinergique P2Y11 dans la modulation des lésions d'Ischémie/Reperfusion myocardique : Role of P2Y11 purinergic receptor on the modulation of myocardial ischemia/reperfusion injuries.

Degree: Docteur es, Sciences de la Vie et de la Santé, 2017, Université François-Rabelais de Tours

URL: http://www.theses.fr/2017TOUR3310

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L’ischémie/reperfusion (I/R) induit des lésions impliquées dans la physiopathologie de la transplantation cardiaque où elles contribuent à augmenter le rejet de greffe. Le stress induit… (more)

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L’ischémie/reperfusion (I/R) induit des lésions impliquées dans la physiopathologie de la transplantation cardiaque où elles contribuent à augmenter le rejet de greffe. Le stress induit par l’ischémie entraîne la libération d’ATP conduisant à l’activation de récepteurs purinergiques (P2R) dont l’expression est établie au niveau cardiaque et immunitaire. L’objectif de ce travail a été d’explorer l’effet de la signalisation P2R sur le phénotype des cellules dendritiques (DCs) et la réponse des cardiomyocytes (CM) à l’I/R. Nous avons montré que la récepteur P2Y11 (P2Y11R) avait une action immunomodulatrice sur les DCs en diminuant la sécrétion d’IL-6 et IL-12 et en inhibant la polarisation de la réponse adaptative vers Th1. Le post-conditionnement pharmacologique ciblant P2Y11R a apporté une protection efficace sur les CM en limitant le stress oxydant et en activant la PKCe connue pour inhiber l’ouverture du mPTP. Les effets protecteurs et immunomodulateurs de P2Y11R se sont confirmés in vivo en diminuant le rejet allogénique dans un modèle murin de transplantation cardiaque hétérotopique. Nos résultats suggèrent que P2Y11R pourrait être une cible thérapeutique apportant des effets bénéfiques en transplantation cardiaque.

Ischemia/reperfusion (I/R) injuries are involved in the pathophysiology of heart transplantation where they will increase graft rejection. Ischemia generates cellular stress leading to ATP release in the extracellular medium that may activate purinergic receptors (P2R) expressed by cardiomyocytes and immune cells. Therefore, these receptors may play important regulatory roles. The aim of this study was to investigate the effect of P2R signaling on dendritic cells phenotype (DCs) and cardiomyocyte (CM) response to I/R. We showed that P2Y11 receptor (P2Y11R) exhibited an immunomodulatory role in DCs by decreasing release of IL-6 and IL-12 and inhibiting polarization of the adaptive response towards Th1. Pharmacological post-conditioning targeting P2Y11R provided effective protection to CM by limiting oxidative stress and activating PKCe known to inhibit the opening of the mPTP. The protective and immunomodulatory effects of P2Y11R stimulation were confirmed in vivo by the decrease of allogeneic acute rejection in a murine model of heterotopic heart transplantation. In conclusion, our results strongly suggest that P2Y11R may be a promising therapeutic target providing beneficial effects in cardiac transplantation.

Advisors/Committee Members: Babuty, Dominique (thesis director).

Subjects/Keywords: Ischémie/Reperfusion; Cellule dendritique; Cardiomyocyte; Récepteur P2Y11; Immunomodulation; Cardioprotection; Transplantation; Ischemia/Reperfusion; Dendritic cell; Cardiomyocyte; P2Y11 receptor; Immunomodulation; Cardioprotection; Transplantation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Benoist, L. (2017). Rôle du récepteur purinergique P2Y11 dans la modulation des lésions d'Ischémie/Reperfusion myocardique : Role of P2Y11 purinergic receptor on the modulation of myocardial ischemia/reperfusion injuries. (Doctoral Dissertation). Université François-Rabelais de Tours. Retrieved from http://www.theses.fr/2017TOUR3310

Chicago Manual of Style (16^th Edition):

Benoist, Lauriane. “Rôle du récepteur purinergique P2Y11 dans la modulation des lésions d'Ischémie/Reperfusion myocardique : Role of P2Y11 purinergic receptor on the modulation of myocardial ischemia/reperfusion injuries.” 2017. Doctoral Dissertation, Université François-Rabelais de Tours. Accessed January 23, 2021. http://www.theses.fr/2017TOUR3310.

MLA Handbook (7^th Edition):

Benoist, Lauriane. “Rôle du récepteur purinergique P2Y11 dans la modulation des lésions d'Ischémie/Reperfusion myocardique : Role of P2Y11 purinergic receptor on the modulation of myocardial ischemia/reperfusion injuries.” 2017. Web. 23 Jan 2021.

Vancouver:

Benoist L. Rôle du récepteur purinergique P2Y11 dans la modulation des lésions d'Ischémie/Reperfusion myocardique : Role of P2Y11 purinergic receptor on the modulation of myocardial ischemia/reperfusion injuries. [Internet] [Doctoral dissertation]. Université François-Rabelais de Tours; 2017. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2017TOUR3310.

Council of Science Editors:

Benoist L. Rôle du récepteur purinergique P2Y11 dans la modulation des lésions d'Ischémie/Reperfusion myocardique : Role of P2Y11 purinergic receptor on the modulation of myocardial ischemia/reperfusion injuries. [Doctoral Dissertation]. Université François-Rabelais de Tours; 2017. Available from: http://www.theses.fr/2017TOUR3310

30. Lasoudris, Fanette. Immunosuppression associée à l’enzyme interleukine-4 induced gene 1 (IL4I1) : régulation de l’expression dans les cellules humaines et rôle dans l’échappement tumoral à la réponse immune dans un modèle murin : Immunosuppression induced by Interleukin-4 Induced gene 1 (IL4I1) : Regulation of expression in human cells and role in tumor escape from the immune response in a murine model.

Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2011, Université Paris-Est

URL: http://www.theses.fr/2011PEST0089

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La protéine IL4I1 est une enzyme sécrétée dont l’activité L-amino acide oxydase vis-à-visde la phénylalanine inhibe la prolifération des lymphocytes T in vitro (Boulland et… (more)

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La protéine IL4I1 est une enzyme sécrétée dont l’activité L-amino acide oxydase vis-à-visde la phénylalanine inhibe la prolifération des lymphocytes T in vitro (Boulland et al, Blood 2007).Comme d’autres enzymes immunosuppressives, elle est exprimée dans les tumeurs au niveau descellules myéloïdes et/ou des cellules tumorales (Carbonnelle-Puscian et al, Leukemia 2009). Le but decette thèse a été de caractériser les conditions d’expression d’IL4I1 et de comprendre son rôle dans lecancer.Nous avons montré que les macrophages et les cellules dendritiques représentent la principalesource d’IL4I1 in vitro et dans des lésions inflammatoires chroniques. L’expression d’IL4I1 dans lesphagocytes mononucléés est induite par les interférons ou les ligands de TLR, activant respectivementSTAT1 et NF-kB, tandis que les lymphocytes B expriment des niveaux nettement plus faibles d’IL4I1sous le contrôle de la voie IL-4/STAT6 et de la voie CD40/NFkB. L’expression d’IL4I1 par des cellulesmonocytaires inhibe la production de cytokines Th1 et pourrait donc contribuer à la régulation del’inflammation Th1 in vivo.Dans un modèle murin de cancer, l’expression d’IL4I1 facilite le développement tumoral endiminuant la réponse T cytotoxique spécifique de la tumeur. Ceci est observé à des niveaux d’activitéIL4I1 proches de ceux mesurés dans des tumeurs humaines, suggérant qu’IL4I1 puisse contribuer àl’échappement des tumeurs au système immunitaire chez l’homme. Nous avons développé plusieursmutants d’IL4I1, afin d’évaluer l’impact de l’activité enzymatique versus celui de l’éventuelle liaison del’enzyme à un récepteur, dans l’effet protumoral observé. Un de ces mutants est actuellementdisponible pour une étude chez la souris.Nos résultats installent définitivement IL4I1 dans le panorama des enzymesimmunosuppressives associées au cancer et ouvrent la voie au développement d’inhibiteursspécifiques comme outils thérapeutiques

The IL4I1 protein is a secreted L-amino acid oxidase, which inhibits T cell proliferationthrough phenylalanine degradation in vitro (Boulland et al, Blood 2007). Similar to previously describedimmunosuppressive enzymes, IL4I1 is expressed in cancer by myeloid cells and/or tumor cells(Carbonnelle-Puscian et al, Leukemia 2009). The aim of this work was to characterize the cells andstimuli associated with IL4I1 expression and to decipher its role in cancer.We showed that macrophages and dendritic cells are the main source of IL4I1 in vitro and inchronic inflammatory lesions. IL4I1 expression in mononuclear phagocytes is induced by interferons orTLR ligands, which act through STAT1 and NFkB respectively. Conversely, B cells express dramaticallylower levels of IL4I1 under the control of IL-4/STAT6 and CD40/NFkB. IL4I1 expression by monocyticcells inhibits the production of Th1 cytokines and may thus contribute to Th1 inflammation control invivo.In a murine model of cancer, IL4I1 expression facilitates tumor development by depressing thetumor specific cytotoxic T cell response. This is observed for IL4I1 activity levels in the…

Advisors/Committee Members: Gaulard, Philippe (thesis director).

Subjects/Keywords: Interleukin-4 induced gene 1; Immunomodulation; Echappement tumoral; Enzyme immunosuppressive; Interleukin-4 induced gene 1; Immunomodulation; Tumor escape; Immunosuppressive Enzyme

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lasoudris, F. (2011). Immunosuppression associée à l’enzyme interleukine-4 induced gene 1 (IL4I1) : régulation de l’expression dans les cellules humaines et rôle dans l’échappement tumoral à la réponse immune dans un modèle murin : Immunosuppression induced by Interleukin-4 Induced gene 1 (IL4I1) : Regulation of expression in human cells and role in tumor escape from the immune response in a murine model. (Doctoral Dissertation). Université Paris-Est. Retrieved from http://www.theses.fr/2011PEST0089

Chicago Manual of Style (16^th Edition):

Lasoudris, Fanette. “Immunosuppression associée à l’enzyme interleukine-4 induced gene 1 (IL4I1) : régulation de l’expression dans les cellules humaines et rôle dans l’échappement tumoral à la réponse immune dans un modèle murin : Immunosuppression induced by Interleukin-4 Induced gene 1 (IL4I1) : Regulation of expression in human cells and role in tumor escape from the immune response in a murine model.” 2011. Doctoral Dissertation, Université Paris-Est. Accessed January 23, 2021. http://www.theses.fr/2011PEST0089.

MLA Handbook (7^th Edition):

Lasoudris, Fanette. “Immunosuppression associée à l’enzyme interleukine-4 induced gene 1 (IL4I1) : régulation de l’expression dans les cellules humaines et rôle dans l’échappement tumoral à la réponse immune dans un modèle murin : Immunosuppression induced by Interleukin-4 Induced gene 1 (IL4I1) : Regulation of expression in human cells and role in tumor escape from the immune response in a murine model.” 2011. Web. 23 Jan 2021.

Vancouver:

Lasoudris F. Immunosuppression associée à l’enzyme interleukine-4 induced gene 1 (IL4I1) : régulation de l’expression dans les cellules humaines et rôle dans l’échappement tumoral à la réponse immune dans un modèle murin : Immunosuppression induced by Interleukin-4 Induced gene 1 (IL4I1) : Regulation of expression in human cells and role in tumor escape from the immune response in a murine model. [Internet] [Doctoral dissertation]. Université Paris-Est; 2011. [cited 2021 Jan 23]. Available from: http://www.theses.fr/2011PEST0089.

Council of Science Editors:

Lasoudris F. Immunosuppression associée à l’enzyme interleukine-4 induced gene 1 (IL4I1) : régulation de l’expression dans les cellules humaines et rôle dans l’échappement tumoral à la réponse immune dans un modèle murin : Immunosuppression induced by Interleukin-4 Induced gene 1 (IL4I1) : Regulation of expression in human cells and role in tumor escape from the immune response in a murine model. [Doctoral Dissertation]. Université Paris-Est; 2011. Available from: http://www.theses.fr/2011PEST0089

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