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You searched for subject:(hBD3). Showing records 1 – 3 of 3 total matches.

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University of Edinburgh

1. McGlasson, Sarah Louise. Regulation of the innate immune system.

Degree: PhD, 2015, University of Edinburgh

The innate immune system is the first line of defence against pathogen invasion. The range of diseases that are caused by deficiencies in or deregulation of the innate immune system illustrates the importance of maintaining an effective balance between clearance of infectious agents and minimisation of inflammatory mediated tissue damage. This thesis explores the role of two proteins in the regulation of the innate immune system. Primarily, this work investigates the effect of human β-defensin 3 (hBD3) on the response to self-DNA and pathogenic DNA. HBD3 is an antimicrobial peptide (AMP), which has been shown to have a role in regulating the immune response; increased copy number of the region containing the gene for hBD3, DEFB103, is linked to an increased risk of psoriasis. Additionally, a similar cationic AMP, LL37, has been shown to exacerbate the pathogenesis of psoriasis by forming an immunogenic complex with self-DNA. This lead to the hypothesis that hBD3 may also affect the innate immune response to DNA. Therefore this project investigates what effect hBD3 has on the response of the innate immune system to self and pathogenic DNA. Flt-3 dendritic cells were used to show that whilst hBD3 increased cellular uptake of self-DNA, it did not convert self-DNA into an immune stimulus. However, hBD3 significantly exacerbated the response to bacterial DNA in a TLR9-dependent manner, also by increasing cellular uptake into FLDCs. The finding that hBD3 increased cellular uptake of both self- and pathogenic DNA suggests that at sites of infection or increased cell death, where DNA would be found in the extracellular environment, hBD3 may increase uptake into immune cells and could induce an increased immune response. Since increased hBD3 expression is induced by inflammatory stimuli, this process would cause a positive feedback loop of inflammation during bacterial infections. In conclusion, hBD3’s role in regulating the innate immune response to DNA is at the ligand-receptor level rather than affecting signalling pathways. Furthermore, hBD3 promotes the innate immune response to bacterial DNA by increasing the efficiency of cellular uptake possibly by inducing DNA aggregation. These results implicate a possible role for hBD3 in the earliest stages of psoriatic plaque development, which is often initiated or exacerbated by an infection, and this could be investigated further. Secondly, I investigated the innate immune function of an E3 ubiquitin ligase (E3L) not previously associated with human disease. Mutations in E3L have been identified in three microcephalic primordial dwarfism families; these patients also presented with recurrent respiratory illnesses. E3L has been implicated in the regulation of the innate immune system via interactions with signalling pathways downstream of the receptor, though its role is not clear. We hypothesised that E3L had a dual role both in regulating growth and cell division and in regulating the immune system. Primary patient fibroblasts did not demonstrate an altered cytokine response…

Subjects/Keywords: 616.07; immune system; human ß-defensin 3; hBD3; ligand-receptor; psoriatic plaque development; E3 ubiquitin ligase; E3L; pathogenic inflammation

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

APA (6th Edition):

McGlasson, S. L. (2015). Regulation of the innate immune system. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/17911

Chicago Manual of Style (16th Edition):

McGlasson, Sarah Louise. “Regulation of the innate immune system.” 2015. Doctoral Dissertation, University of Edinburgh. Accessed January 25, 2021. http://hdl.handle.net/1842/17911.

MLA Handbook (7th Edition):

McGlasson, Sarah Louise. “Regulation of the innate immune system.” 2015. Web. 25 Jan 2021.

Vancouver:

McGlasson SL. Regulation of the innate immune system. [Internet] [Doctoral dissertation]. University of Edinburgh; 2015. [cited 2021 Jan 25]. Available from: http://hdl.handle.net/1842/17911.

Council of Science Editors:

McGlasson SL. Regulation of the innate immune system. [Doctoral Dissertation]. University of Edinburgh; 2015. Available from: http://hdl.handle.net/1842/17911

2. Huang, Shu-Mei. Effects of high glucose on keratinocyte functions: focusing on the impaired diabetic wound healing.

Degree: PhD, Biological Sciences, 2015, NSYSU

Diabetes mellitus is characterized by elevated plasma glucose and increased rate of skin infection. Altered immune responses have been suggested to contribute to this prevalent complication. High glucose treatment reduced human β-defensin-3 (hBD3) expression of cultured keratinocytes. This pathogenic process involved inhibition of p38MAPK signaling, an event that resulted from increased formation of advanced glycation end product and showed worse anti-Staphylococcus aureus activity. In addition, high-glucose cultivated keratinocytes expressed reduced levels of human β-defensin-2 (hBD2) and pSTAT-1. Besides the impact on keratinocyte cultured under high glucose, the suboptimal interaction between keratinocytes and inflammatory cells also contributed to impaired diabetic wound healing. High-glucose environment enhanced interleukin (IL)-8 production via EGFR-ERK pathway in a ROS-dependent manner in keratinocytes. Treating diabetic rats with neutrophil inhibitor improved the healing. On the other hands, high glucose cultivated monocytes have significantly reduced production of IL-22, a molecule that is responsible for promoting keratinocyte migration. In summary, high glucose environment impared keratinocyte function directly or indirectly that contributed to impaired diabetic wound healing, and focusing on these defects will present a therapeutic approach to promote diabetic healing. Advisors/Committee Members: Ching-Shuang Wu (chair), Lan, Cheng-Che (chair), Liu, Jong-Kang (chair), Chao, David (committee member), Chen, Gwo-Shing (chair).

Subjects/Keywords: hBD3; interleukin-8; keratinocyte; hBD2; high glucose; interleukin-22

…培養對角質細胞分化的影響情形 ….…24 圖 2-6 不同糖濃度培養對角質細胞 hBD3 產量的影響 …. .25 圖 2-7 角質細胞在… …p38MAPK 抑制下的 hBD3 表現 …26 圖 2-8 高糖等滲透壓組的 hBD3 表現 ..27 圖 2-9 經過不同糖濃度培養… …後之角質細胞培養液對抗 S. aureus 的活性 28 圖 2-10 角質細胞經 hBD3 基 靜默後之細胞培養液對抗 S. aureus 的活性 …29 圖 2-11… …不同糖濃度培養對角質細胞 TLR-2 表現的影響 …30 圖 2-12 角質細胞使用 TLR-2 促進劑後的 hBD3 表現 31 圖 2… …圖 2-15 p38MAPK 抑制劑的使用抑制了 TLR-2 促進劑刺激 hBD3 產生的效應…34 圖 2-16 角質細胞培養時 入 AGE 培養 2 天後的 hBD3 產量… 

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

APA (6th Edition):

Huang, S. (2015). Effects of high glucose on keratinocyte functions: focusing on the impaired diabetic wound healing. (Doctoral Dissertation). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0823115-001730

Chicago Manual of Style (16th Edition):

Huang, Shu-Mei. “Effects of high glucose on keratinocyte functions: focusing on the impaired diabetic wound healing.” 2015. Doctoral Dissertation, NSYSU. Accessed January 25, 2021. http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0823115-001730.

MLA Handbook (7th Edition):

Huang, Shu-Mei. “Effects of high glucose on keratinocyte functions: focusing on the impaired diabetic wound healing.” 2015. Web. 25 Jan 2021.

Vancouver:

Huang S. Effects of high glucose on keratinocyte functions: focusing on the impaired diabetic wound healing. [Internet] [Doctoral dissertation]. NSYSU; 2015. [cited 2021 Jan 25]. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0823115-001730.

Council of Science Editors:

Huang S. Effects of high glucose on keratinocyte functions: focusing on the impaired diabetic wound healing. [Doctoral Dissertation]. NSYSU; 2015. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0823115-001730

3. Dhingra, Harpreet. PEPTIDE ENGINEERING FOR DEVELOPMENT OF ANTIMICROBIALS AGAINST Mannheimia haemolytica.

Degree: 2013, University of Saskatchewan

Mannheimia haemolytica (M. haemolytica)-induced bovine respiratory disease causes millions of dollars in economic losses to Canadian cattle industry. Contemporary management strategies built around the use of antimicrobials are proving to be increasingly unavailing and lead to drug residues in meat which may contribute to the development of multi drug resistant bacteria. Many M. haemolytica vaccines are effective in stimulating antibody responses but studies of vaccina-tion in young calves and the cattle exposed to M. haemolytica (high-risk cattle) have shown poor vaccine efficacy. Antimicrobial peptides (AMPs) may help in the management of respiratory disease caused by M. haemolytica while minimizing the risk of drug residues in animal-derived food products. AMPs are positively charged molecules that can kill bacteria primarily through the electrostatic interactions with the anionic bacterial lipid bilayer. Since the primary target of AMPs is the bac-terial surface charge, which is evolutionarily conserved, the development of resistance towards AMPs seems less likely. These peptides hold potential to replace or reduce the use of antibiotics. Human β-Defensin 3 (HBD3) and Microcin J25 (MccJ25) are cationic peptides that have shown good activity against many Gram-negative bacteria. Five peptides, namely native HBD3, three synthetic HBD3 analogues (28 amino acid, 20AA, and 10AA), and MccJ25 were selected for microbicidal activity against M. haemolytica. Three C-terminal analogues of HBD3 with all cysteines replaced with valines were manually synthesized using solid phase peptide synthesis (SPPS). In all the three analogue, replacement of cysteine with valine rendered them linear and increased their antibacterial activity. Minimum Bactericidal concentration (MBC) assays were performed with the final inoculum size of 1-5x105 cells/ml, with the exception of the 10AA analogue which was incubated with 104 cells/ml final inoculum size. The antimicrobial assay showed that M. haemolytica was intermediately sensitive to HBD3, 28AA and 20AA analogue with an MBC of 50 µg/ml. MccJ25 had limited effect with an MBC greater than 100 µg/ml. The MBC value of 6.3 µg/ml achieved with the 10AA analogue is likely a result of lower final inoculum size. AMPs have several immunomodulatory functions, and these peptides can act as chemoattractant, induce cytokine release that in turn leads to chemotaxis of monocytes and neutrophils. Since neutrophils play an important role in the pathogenesis of BRD, the chemotactic effect of HBD3, 20AA and 28AA peptides on bovine neutrophils was studied using Boyden chamber. Peripheral blood neutrophils isolated from normal healthy cattle showed chemotaxis towards HBD3 and 20AA peptides (P<0.05) but not towards 28AA analogue. Co-incubation of neutrophils with any of the peptides did not affect their chemotaxis towards N-formyl-L-methionyl-L-leucyl-phenylalanine (fMLP). Based on these data, it can be concluded that HBD3 and its analogues showed antimicrobial ef-fects against M. haemolytica but MccJ25 had… Advisors/Committee Members: Singh, Baljit, Kaur, Kamaljit, Loewen, Matthew, Singh, Jaswant.

Subjects/Keywords: M. haemolytica; Human β-Defensin 3 (HBD3) and Microcin J25 (MccJ25); cationic peptides; solid phase peptide synthesis; Minimum Bactericidal concentration; Boyden chamber; bovine neutrophils; chemotaxis

…64 7.1.2. HBD3… …65 7.1.3. HBD3 Analogues… …scheme for 10AA and 20AA HBD3 analogues. ............................... 40 Table 6.2. Number… …of colony forming units after treatment with HBD3. The tissue culture dishes were… …47 Table 6.3. Number of colony forming units after treatment with HBD3 20 AA analogue. The… 

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

APA (6th Edition):

Dhingra, H. (2013). PEPTIDE ENGINEERING FOR DEVELOPMENT OF ANTIMICROBIALS AGAINST Mannheimia haemolytica. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/ETD-2013-10-1332

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

Chicago Manual of Style (16th Edition):

Dhingra, Harpreet. “PEPTIDE ENGINEERING FOR DEVELOPMENT OF ANTIMICROBIALS AGAINST Mannheimia haemolytica.” 2013. Thesis, University of Saskatchewan. Accessed January 25, 2021. http://hdl.handle.net/10388/ETD-2013-10-1332.

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

MLA Handbook (7th Edition):

Dhingra, Harpreet. “PEPTIDE ENGINEERING FOR DEVELOPMENT OF ANTIMICROBIALS AGAINST Mannheimia haemolytica.” 2013. Web. 25 Jan 2021.

Vancouver:

Dhingra H. PEPTIDE ENGINEERING FOR DEVELOPMENT OF ANTIMICROBIALS AGAINST Mannheimia haemolytica. [Internet] [Thesis]. University of Saskatchewan; 2013. [cited 2021 Jan 25]. Available from: http://hdl.handle.net/10388/ETD-2013-10-1332.

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

Council of Science Editors:

Dhingra H. PEPTIDE ENGINEERING FOR DEVELOPMENT OF ANTIMICROBIALS AGAINST Mannheimia haemolytica. [Thesis]. University of Saskatchewan; 2013. Available from: http://hdl.handle.net/10388/ETD-2013-10-1332

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

.