Involvement of Fas/Fas ligand system-mediated apoptosis in the development of concanavalin A-induced hepatitis

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Abstract
Concanavalin A (Con A)‐induced hepatitis is an experimental hepatitis model in which hepatic injury is caused by the action of cytokines produced by T cells. Using IFN‐γ‐deficient mice, we previously demonstrated that IFN‐γ plays a central role in Con A‐induced hepatitis. Here, we show that development of the disease is completely suppressed in gld/gld mice, in which Fas ligand is defective. In contrast, suppression of the disease in lpr/lpr mice was incomplete, since a small amount of the fas mRNA was produced in these mice. The data indicate that activation of the Fas/Fas ligand system is a necessary step in the development of Con A‐induced hepatitis. Furthermore, we found that not only fas but also caspase‐1 expression was reduced in IFN‐γ‐deficient mice. Since caspase‐1 is an integral component of Fas signal transduction, these observations suggest that IFN‐γ‐induced activation of both fas and caspase‐1 expression causes enhancement of hepatocyte apoptosis resulting in the development of hepatitis.