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Please use this identifier to cite or link to this item:
http://hdl.handle.net/1974/6566
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| Title: | Lipopolysaccharide-Mediated Regulation of IL-17 Receptor Levels in Human Monocytes |
| Authors: | ZHANG, Xiubo |
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| Keywords: | IL-17R
human monocytes
LPS
receptor regulation |
| Issue Date: | 2011 |
| Series/Report no.: | Canadian theses |
| Abstract: | IL-17 promotes inflammation through the recruitment of monocytes and induction of various chemokines and inflammatory cytokines. Monocytes respond to IL-17 through the heteromeric IL-17 receptor (IL-17R) composed of subunits IL-17RA and IL-17RC. Together, monocytes and IL-17 amplify inflammation. Controlling the cellular response to IL-17 is crucial to prevent hyperactivation of inflammatory responses, which could lead to chronic inflammatory diseases. The cellular response to increased IL-17 levels may be limited by controlling the receptor levels. Before we understand how monocytes respond to IL-17 during infection, we must first characterize the expression of IL-17R in these cells in response to LPS, a well-characterized pro-inflammatory signal. The aim of this study is to understand the mechanisms which regulate IL-17R levels in human monocytes. IL-17R mRNA and protein levels were measured in response to LPS by RT-PCR and Western blot analysis in primary human monocytes, peripheral blood mononuclear cells (PBMC), and the human monocytic cell line, THP-1. LPS enhanced IL-17RA and RC transcript levels in monocytes and PBMC. In contrast, IL-17RA protein levels decreased with LPS treatment in these cells. Investigation into mechanisms regulating IL-17RA protein levels lead to the observation that IL-17RA undergoes receptor degradation in response to LPS. This work identifies for the first time that 1) LPS enhances transcript levels of IL-17R and 2) after LPS treatment, IL-17RA protein levels are reduced via an endosome-dependent degradation pathway. |
| Description: | Thesis (Master, Microbiology & Immunology) -- Queen's University, 2011-06-21 11:53:28.706 |
| URI: | http://hdl.handle.net/1974/6566 |
| Appears in Collections: | Queen's Theses & Dissertations
Microbiology & Immunology Graduate Theses
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