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INTERLEUKIN-10 RECEPTOR DYSFUNCTION IN PERITONEAL MACROPHAGES BY TOLL-LIKE RECEPTOR LIGANDS

Interleukin-10 (IL-10) is a pleiotropic cytokine which limits inflammatory responses by balancing the hosts immune response against infection. Mammalian Toll-like receptors (TLRs) are pattern recognition receptors that recognize specific molecular pattens on microbial pathogens and activate intracellular signaling via the transcription factors NF-B and IRF-3. In this study we evaluate the contribution of the TLR ligands Poly I:C, Pam3CSK4, LPS and LTA to IL-10 receptor dysfunction in murine peritoneal macrophages (PM). We examine how these ligands are able to alter IL-10 mediated STAT3 phosphorylation and CCR5 gene expression in PM. The ability of Poly I:C and Pam3CSK4 to alter the immunosuppressive activity of IL-10 in C2-ceramide stimulated PM is also examined. The results of our study indicate a delayed inhibition of IL-10 mediated activation of STAT3 by LPS, LTA, Poly I:C and Pam3CSK4. The CCR5 gene expression experiments demonstrate that LPS was able to down-regulate IL-10 induced CCR5 mRNA expression in PM.

Identiferoai:union.ndltd.org:uky.edu/oai:uknowledge.uky.edu:gradschool_theses-1420
Date01 January 2005
CreatorsBhattacharyya, Surjya
PublisherUKnowledge
Source SetsUniversity of Kentucky
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceUniversity of Kentucky Master's Theses

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