Critical involvement of Th1-related cytokines in renal injuries induced by ischemia and reperfusion.
Renal ischemia and reperfusion injury (IRI) is considered an inflammatory syndrome. To move forward in its pathogenesis, we exploited the role of several cytokines on renal damages triggered by IRI. Specifically to evaluate the role of Th1 immune profile in this system, IL-12, IFN-gamma, and IFN-gamma/IL-12 deficient (KO) mice on C57BL/6 background and their controls were subjected to IRI. In each group, blood and kidney samples were harvested. Renal function was evaluated by serum creatinine and renal morphometric analyses. Gene expression of IL-6 and HO-1 were also investigated by Q-PCR. IFN-gamma KO animals presented the highest impairment in renal function compared to controls. Conversely, IL-12 KO animals were absolutely protected and, in a lesser extent, IFN-gamma/IL-12 KO double knockout was also protected from IRI. Gene expression analyses showed higher expression of HO-1, a cytoprotective gene, and IL-6, a pro-inflammatory cytokine, in IFN-gamma deficient animals subjected to IRI. Our results confirm that Th1 related cytokines such as IL-12 and IFN-gamma are critically involved in renal ischemia and reperfusion injury.
de Paiva
Vanessa Nunes
VN
Laboratory of Clinical and Experimental Immunology. Nephrology Division, Department of Medicine, Universidade Federal de São Paulo UNIFESP-EPM, São Paulo, Brazil.
Monteiro
Rebecca M M
RM
Marques
Vilmar de Paiva
Vde P
Cenedeze
Marcos Antonio
MA
Teixeira
Vicente de P A
Vde P
dos Reis
Marlene A
MA
Pacheco-Silva
Alvaro
A
Câmara
Niels O S
NO
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D051547:Heme Oxygenase-1 / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007511:Ischemia / Q000276:immunology*; D007668:Kidney / Q000098:blood supply* / Q000276:immunology; D007674:Kidney Diseases / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000276:immunology / Q000378:metabolism; D015427:Reperfusion Injury / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma; D051547:Heme Oxygenase-1