Suppression of concanavalin A-induced hepatitis in IFN-gamma(-/-) mice, but not in TNF-alpha(-/-) mice: role for IFN-gamma in activating apoptosis of hepatocytes.
Con A-induced hepatitis (Con A-hepatitis) is a hepatitis model in which hepatic injury is supposed to be caused by cytokines from activated T cells. To elucidate the pathogenesis of this disease, we analyzed the roles of IFN-gamma and TNF-alpha using deficient mice of these cytokines. Development of hepatitis was reduced significantly in IFN-gamma(-/-) mice, while susceptibility of TNF-alpha(-/-) mice was not changed. Interestingly, apoptotic cell death was observed in the affected livers of control or TNF-alpha(-/-) mice, but not in those of IFN-gamma(-/-) mice. Fas mRNA expression was increased in the livers of hepatitis mice, but less abundantly in those of IFN-gamma(-/-) mice. Since apoptosis of liver cells was rarely observed in Con A-treated lpr/lpr mice, involvement of the Fas-Fas ligand system in this apoptotic process was suggested. These observations suggest that IFN-gamma plays a central role in Con A-hepatitis by activating Fas-induced apoptosis of liver cells.
Tagawa
Y
Y
Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Japan.
Sekikawa
K
K
Iwakura
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D002678:Chimera / Q000276:immunology; D003208:Concanavalin A / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000276:immunology; D005818:Genetic Engineering; D006520:Hepatitis, Animal / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D007108:Immune Tolerance / Q000187:drug effects / Q000235:genetics*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency* / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D037121:Plant Lectins; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency* / Q000235:genetics; D019014:fas Receptor / Q000502:physiology
D037121:Plant Lectins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D003208:Concanavalin A; D007371:Interferon-gamma