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.

Y Tagawa, K Sekikawa, Y Iwakura - Journal of immunology …, 1997 - journals.aai.org
Y Tagawa, K Sekikawa, Y Iwakura
Journal of immunology (Baltimore, Md.: 1950), 1997journals.aai.org
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 …
Abstract
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.
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