The role of toll-like receptor 4 in cisplatin-induced renal injury.
BACKGROUND
Toll-like receptors recognize pattern-associated molecules found in pathogens as well as in endogen cells and in matrix degradation products. Despite the effectiveness of cisplatin against various solid tumors the administered dose is limited by its nephrotoxicity, namely, induction of tubular cell apoptosis. Herein, we investigated whether the cell toxicity of cisplatin was mediated by toll-like receptor 4 signaling.


METHODS
C3H/He J (Toll-like receptor 4 deficient) and C3H/HePas (control) were treated with cisplatin (20 mg/kg). We evaluated renal function as well as expression of (HO-1) heme oxygenase 1 and MCP-1 mRNAs.


RESULTS
Animals deficient in Toll-like receptor 4 showed less renal dysfunction after cisplatin therapy, which was more evident at later time points. Moreover, MCP-1 mRNA expression in kidneys from these animals were lower than controls, mainly at 96 hours after treatment. No differences were seen in HO-1 mRNA expression.


CONCLUSIONS
These results suggested that cisplatin-induced renal toxicity is mediated in part though toll-like receptor 4.
Cenedeze
M A
MA
Laboratório de Imunologia Clínica e Experimental, Division of Nephrology, Universidade Federal de São Paulo, Escola Paulista de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Gonçalves
G M
GM
Feitoza
C Q
CQ
Wang
P M H
PM
Damião
M J
MJ
Bertocchi
A P F
AP
Pacheco-Silva
A
A
Câmara
N O S
NO
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics; D002945:Cisplatin / Q000633:toxicity*; D051547:Heme Oxygenase-1 / Q000235:genetics; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology*; D007677:Kidney Function Tests; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000172:deficiency* / Q000502:physiology*
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051547:Heme Oxygenase-1; D002945:Cisplatin