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You searched for +publisher:"Temple University" +contributor:("Jensen, Liselotte"). Showing records 1 – 3 of 3 total matches.

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Temple University

1. Nattkemper, Leigh. MEDIATORS AND RECEPTORS OF CHRONIC ITCH IN PRIMATES AND HUMANS.

Degree: PhD, 2015, Temple University

Biomedical Sciences

Chronic itch has a significant impact on quality of life for millions of patients worldwide, on a level comparable to that of chronic pain. Yet, although there are a host of effective drugs available for pain, there are no therapies that specifically target chronic itch. Current experimental approaches to investigate the pathogenesis of chronic pruritus and to test novel therapeutic agents are largely limited to rodent models. However, rodent models display significant dermatological, neurophysiological, and immunological differences from humans with chronic itch. The disadvantages of the current rodent paradigms call for the design of a valid primate model of chronic itch. For four years, we have monitored scratching behavior in a primate colony (n=35) of Cynomolgus macaques (Macaca fascicularis) suffering from idiopathic chronic itch. By comparing molecular and genetic analyses of the primates’ skin to their quantified scratching behavior, we attempted to characterize the underlying mechanisms of chronic itch in this model. Furthermore, the expression of itch-related proteins was examined in both the primate model and in humans with pruritic diseases. The first aim of the study was to characterize the underlying molecular and genetic basis of chronic itch in the primate model. We were able to distinguish specific peripheral targets related to pruritus by correlating the genetic and protein expression results to the primates’ scratching severity. In Aim 1a, RNA-sequencing was performed on skin biopsies from the primates to identify differentially expressed genes in pruritic, lichenified versus non-pruritic, non-lichenified skin. These results were then correlated to the quantified primate scratching behavior. This led to the identification of over 400 genes that were differentially expressed in the skin based on scratching intensity. Many of these differentially expressed transcripts were associated with sensory nerve fibers, keratinocytes, mast cells, or lymphocytes. Selected genes that were overexpressed and correlated to itch intensity were then targeted for immunohistochemical and proteomic analysis in Aim 1b. Immunohistochemical examination of the primate skin biopsies revealed that histamine levels were not elevated in primates that exhibited increased scratching behavior. However, mast cells containing tryptase were significantly increased in the skin of primates with severe scratching as compared to primates with mild scratching. The increased levels of gastrin-releasing peptide and substance P in lichenified skin were also found to be correlated to the primates’ scratching behavior. Of note, transient receptor potential channels V1, V3, and A1 were increased in the epidermis of primate skin, but the numbers of TRPV1+ and TRPA1+ nerve fibers were not significantly different between lichenified and non-lichenified skin. Transcriptome analysis of the opioid receptors and their ligands showed that primates with severe scratching behavior had a significant imbalance between the µ- and…

Advisors/Committee Members: Yosipovitch, Gil;, Barbe, Mary F., Jensen, Liselotte, Cowan, Alan, Hoon, Mark;.

Subjects/Keywords: Neurosciences; Molecular biology; Genetics;

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

APA (6th Edition):

Nattkemper, L. (2015). MEDIATORS AND RECEPTORS OF CHRONIC ITCH IN PRIMATES AND HUMANS. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,360207

Chicago Manual of Style (16th Edition):

Nattkemper, Leigh. “MEDIATORS AND RECEPTORS OF CHRONIC ITCH IN PRIMATES AND HUMANS.” 2015. Doctoral Dissertation, Temple University. Accessed September 25, 2020. http://digital.library.temple.edu/u?/p245801coll10,360207.

MLA Handbook (7th Edition):

Nattkemper, Leigh. “MEDIATORS AND RECEPTORS OF CHRONIC ITCH IN PRIMATES AND HUMANS.” 2015. Web. 25 Sep 2020.

Vancouver:

Nattkemper L. MEDIATORS AND RECEPTORS OF CHRONIC ITCH IN PRIMATES AND HUMANS. [Internet] [Doctoral dissertation]. Temple University; 2015. [cited 2020 Sep 25]. Available from: http://digital.library.temple.edu/u?/p245801coll10,360207.

Council of Science Editors:

Nattkemper L. MEDIATORS AND RECEPTORS OF CHRONIC ITCH IN PRIMATES AND HUMANS. [Doctoral Dissertation]. Temple University; 2015. Available from: http://digital.library.temple.edu/u?/p245801coll10,360207


Temple University

2. Rapsinski, Glenn James. Immune Recognition of S. Typhimurium Biofilms via Amyloids and Extracellular DNA.

Degree: PhD, 2016, Temple University

Microbiology and Immunology

Salmonella enterica serovar Typhimurium is an important cause of gastroenteritis in the United States and the developing world. Biofilm growth is an significant mechanism, which S. Typhimurium utilizes to contaminate food products and survive in the environment. Biofilms are also an important part of the infectious process for many pathogenic bacteria. As part of the biofilm, S. Typhimurium produces an extracellular matrix consisting of cellulose, extracellular DNA, and most importantly, the amyloid protein curli. Similar to amyloids associated with human diseases, curli is recognized by the innate immune system through Toll-Like Receptors (TLRs). Here, we studied the immune receptors recognizing curli as well as interactions between eDNA and curli during biofilm development in order to glean a better understanding of these complex bacterial communities and the immune response to them. Recently, our lab demonstrated that curli fibers are recognized by the TLR2/TLR1 complex. CD14 has been shown to be a common adaptor protein for TLR2/TLR1 complex in response to one of its ligands, tri-acylated lipopeptide, Pam3CSK4. In order to study the role of CD14 in the immune receptor complex recognizing curli, we utilized HeLa 57A cells, a human cervical cancer cell line that has a stably transfected luciferase reporter for Nf-κB activation. When these cells were transiently transfected with TLR2 and TLR1 together or with the addition of membrane-bound CD14, NfκB activation was enhanced by the presence of CD14 in response to purified curli, GST-tagged curli subunit (GST-CsgA), and the control lipopeptide Pam3CSK4. Soluble CD14 also increased NfκB activation in response to purified curli. Bone marrow derived macrophages (BMDM) from wild type (C57BL/6) mice produced more IL-6 and nitric oxide in response to stimulation with purified curli, GST-CsgA, and Pam3CSK4, than BMDMs deficient in CD14. Binding assays demonstrated direct binding of curli to all members of this hypothesized trimolecular complex, TLR2, TLR1, and CD14. Utilizing synthetic peptides corresponding to the fourth and fifth repeat of the CsgA monomer, CsgA R4-5, and its modified version, CsgA R4-5N122A deficient in forming amyloid fibers, we also showed that binding to CD14, and CD14 enhancement of IL-6 production required the fibrillar amyloid structure of curli. To study interactions between curli and eDNA in biofilms and the resulting immune response generated to composites formed by these ECM components, we analyzed biofilms of GFP expressing S. Typhimurium using confocal laser scanning microscopy (CLSM). Staining for amyloids with Congo Red revealed the presence of curli in the biofilms and staining with propidium iodide demonstrated the presence of extracellular DNA in the biofilms. Co-staining with TOTO-1, a nucleic acid stain, and Congo Red showed co-localization of the fluorescent signal for these molecules within the biofilms. DNase I treatment of the biofilms produced no significant change in biofilm thickness by confocal…

Advisors/Committee Members: Tukel, Cagla;, Buttaro, Bettina A., Ganea, Doina, Jensen, Liselotte, Soprano, Dianne R.;.

Subjects/Keywords: Microbiology; Immunology;

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

APA (6th Edition):

Rapsinski, G. J. (2016). Immune Recognition of S. Typhimurium Biofilms via Amyloids and Extracellular DNA. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,273605

Chicago Manual of Style (16th Edition):

Rapsinski, Glenn James. “Immune Recognition of S. Typhimurium Biofilms via Amyloids and Extracellular DNA.” 2016. Doctoral Dissertation, Temple University. Accessed September 25, 2020. http://digital.library.temple.edu/u?/p245801coll10,273605.

MLA Handbook (7th Edition):

Rapsinski, Glenn James. “Immune Recognition of S. Typhimurium Biofilms via Amyloids and Extracellular DNA.” 2016. Web. 25 Sep 2020.

Vancouver:

Rapsinski GJ. Immune Recognition of S. Typhimurium Biofilms via Amyloids and Extracellular DNA. [Internet] [Doctoral dissertation]. Temple University; 2016. [cited 2020 Sep 25]. Available from: http://digital.library.temple.edu/u?/p245801coll10,273605.

Council of Science Editors:

Rapsinski GJ. Immune Recognition of S. Typhimurium Biofilms via Amyloids and Extracellular DNA. [Doctoral Dissertation]. Temple University; 2016. Available from: http://digital.library.temple.edu/u?/p245801coll10,273605


Temple University

3. Milora, Katelynn Ann. Characterization of IL-1 and IL-36 Cytokines in Health and Disease.

Degree: PhD, 2017, Temple University

Microbiology and Immunology

Epithelial cells are the first line of defense against invading pathogens and external threats in the environment. Keratinocytes, often not perceived of as immune cells, release cytokines in response to infection or injury to signal danger to neighboring cells and recruit effector leukocytes to prevent further damage to the host. IL-1 and IL-36 cytokines are a group of closely related proteins that share similarities in structure and function and have been shown to play key roles in inflammatory responses of epithelial tissues. While IL-1, consisting of IL-1α and IL-1β, have been widely studied and recognized as pinnacle cytokines in a variety of inflammatory responses, relatively little is understood about IL-36 cytokines since their discovery more than 15 years ago, and how they differ from their better-known IL-1 relatives. IL-36 cytokines, consisting of IL-36α, IL-36β, and IL-36γ, signal through the same receptor, IL-36R, which is expressed most abundantly on epithelial cells. IL-36 proteins garnered attention when it was discovered that a missense mutation in the gene encoding the naturally occurring receptor antagonist, IL-36Ra, was associated with the deadly form of psoriasis, generalized pustular psoriasis (GPP). This disease is characterized by episodic flares of keratinocyte hyperproliferation leading to red scaly lesions all over the body, excessive neutrophil recruitment to the epidermis resulting in pustule formation, and severe fever. Our data presented here demonstrate that IL-36α, but not IL-36β or IL-36γ is critical for the psoriatic phenotype, including epidermal thickening and neutrophil recruitment, generated during a murine model of psoriasis induced by the drug Imiquimod. Furthermore, IL-36α was found to induce IL-1α expression and vice versa through a signaling feedback loop which perpetuated disease. These data provide insight into mechanisms whereby IL-36 signaling can lead to excessive inflammatory effects in patients with pre-existing regulation deficiencies, which can lead to acute flares of disease. Beyond their association with disease, IL-1 has been shown to contribute to anti-bacterial and anti-viral responses of the immune system by upregulating inflammatory signals and chemoattractants. Herpes Simplex Virus-1 (HSV-1) is a human pathogen that has developed several strategies to manipulate elements of the immune system to avoid detection by the host. One such mechanism is the prevention of activation and release of IL-1β from infected cells thereby blocking its pro-inflammatory responses. Our data show that keratinocytes infected with HSV-1 actively release IL-1α to alert danger to neighboring cells to circumvent this blockage of IL-1β signaling. This release of IL-1α initiates recruitment of leukocytes to early HSV-1 microinfection sites resulting in increased protection against disease, as evident by the increased mortality rate of mice deficient in the IL-1 receptor, IL-1R1. This study, for the first time in vivo, demonstrates the ability of IL-1α to…

Advisors/Committee Members: Jensen, Liselotte;, Jennings, Stephen R., Tukel, Cagla, Monestier, Marc, Rall, Glenn F.;.

Subjects/Keywords: Immunology;

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

APA (6th Edition):

Milora, K. A. (2017). Characterization of IL-1 and IL-36 Cytokines in Health and Disease. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,451599

Chicago Manual of Style (16th Edition):

Milora, Katelynn Ann. “Characterization of IL-1 and IL-36 Cytokines in Health and Disease.” 2017. Doctoral Dissertation, Temple University. Accessed September 25, 2020. http://digital.library.temple.edu/u?/p245801coll10,451599.

MLA Handbook (7th Edition):

Milora, Katelynn Ann. “Characterization of IL-1 and IL-36 Cytokines in Health and Disease.” 2017. Web. 25 Sep 2020.

Vancouver:

Milora KA. Characterization of IL-1 and IL-36 Cytokines in Health and Disease. [Internet] [Doctoral dissertation]. Temple University; 2017. [cited 2020 Sep 25]. Available from: http://digital.library.temple.edu/u?/p245801coll10,451599.

Council of Science Editors:

Milora KA. Characterization of IL-1 and IL-36 Cytokines in Health and Disease. [Doctoral Dissertation]. Temple University; 2017. Available from: http://digital.library.temple.edu/u?/p245801coll10,451599

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