Toll-like receptors 2 and 4 in renal ischemia/reperfusion injury.
Toll-like receptors (TLRs) are an evolutionarily conserved family of cell membrane receptors that are part of the innate immunity system playing an important role as a first response to tissue injury. TLR2 and TLR4 are constitutively expressed on renal epithelium, and their expression is enhanced following renal ischemia/reperfusion (I/R) injury. Genetic deletion of either TLR2 or TLR4 protects from renal I/R injury. However, it is not known whether deletion of both combined protects the kidney more than a deletion of either one alone. Therefore, we performed renal I/R injury in mice lacking TLR2, TLR4, and TLR2/4, respectively. Our results demonstrate that there are no significant differences regarding protection from renal I/R injury in TLR2/4((-/-)) compared with either TLR2((-/-)) or TLR4((-/-)) gene-targeted mice as determined by histological evaluation and renal functional parameters. Furthermore, there was no difference in the number of apoptotic tubular cells and in nuclear translocation of nuclear factor kappa-B (NF-kappaB) between the TLR-gene-targeted groups. In parallel, in vitro experiments did not demonstrate an additional effect of the double genetic deletion compared with the single gene deletion with respect to tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 production in hypoxic isolated proximal tubular epithelial cells of the respective animals. In conclusion, a double genetic deletion of TLR2 and TLR4 confers a similar protection following renal I/R injury compared with single deletions of TLR2 and TLR4.
Department of Nephrology, Technical University Munich, Klinikum rechts der Isar, Ismaninger Str. 22, Munich, Germany.
Krisztina
K
Rusai
Daniel
D
Sollinger
Marcus
M
Baumann
Bettina
B
Wagner
Matthias
M
Strobl
Christoph
C
Schmaderer
Marcel
M
Roos
Carsten
C
Kirschning
Uwe
U
Heemann
Jens
J
Lutz
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004195:Disease Models, Animal; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000378:metabolism; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D007674:Kidney Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D015427:Reperfusion Injury / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016209:Interleukin-8; D016328:NF-kappa B; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha