Endogenous ligands for TLR2 and TLR4 are not involved in renal injury following ureteric obstruction.
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.
Chowdhury
Paramit
P
Department of Nephrology and Transplantation, King's College London, Guy's Hospital, London, UK. paramit.chowdhury@kcl.ac.uk
Sacks
Steven Howard
SH
Sheerin
Neil Stephen
NS
D000818:Animals; D005260:Female; D005355:Fibrosis; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014517:Ureteral Obstruction / Q000378:metabolism*
D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha