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Endogenous Ligands for TLR2 and TLR4 Are Not Involved in Renal Injury following Ureteric Obstruction

Lookup NU author(s): Professor Neil SheerinORCiD

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Abstract

Background: Toll-like receptors (TLRs) are a recently described arm of innate immunity. As well as responding to conserved molecular patterns found on pathogens, TLRs can also respond to endogenous ligands. Those described for TLR2 and TLR4 include molecules released following tissue injury including heat shock proteins and matrix proteins. We hypothesised that following injury, TLRs on renal tubular cells are activated by these endogenous ligands, resulting in cytokine production and cellular infiltration which propagate the fibrotic process. Methods: We performed unilateral ureteric obstruction (UUO) in wild-type C57BL/6, TLR2 knockout and TLR4 knockout mice. Gene expression of TGF-beta and TNF-alpha within renal tissue was analysed by real-time PCR. Kidneys were also scored for the level of tubulointerstitial fibrosis, collagen type IV deposition and macrophage infiltration. Results: No significant difference was found in the degree of tubulointerstitial fibrosis, collagen type IV deposition or macrophage infiltration 14 days after UUO between the 3 groups. Renal TNF-alpha and TGF-beta gene expression was also similar in all groups 3 days after UUO. Conclusions: TLR2 and TLR4 do not play a significant role in the development of tubulointerstitial fibrosis following obstruction. Copyright (C) 2010 S. Karger AG, Basel


Publication metadata

Author(s): Chowdhury P, Sacks SH, Sheerin NS

Publication type: Article

Publication status: Published

Journal: Nephron Experimental Nephrology

Year: 2010

Volume: 115

Issue: 4

Pages: E122-E130

Print publication date: 01/01/2010

Date deposited: 08/11/2010

ISSN (print): 1660-2129

ISSN (electronic): 1660-8151

Publisher: S. Karger AG

URL: http://dx.doi.org/10.1159/000313493

DOI: 10.1159/000313493


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