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

Eur J Immunol. 1998 Dec;28(12):4105-13. doi: 10.1002/(SICI)1521-4141(199812)28:12<4105::AID-IMMU4105>3.0.CO;2-8.

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-gamma-deficient mice, we previously demonstrated that IFN-gamma 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 Ipr/Ipr 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-gamma-deficient mice. Since caspase-1 is an integral component of Fas signal transduction, these observations suggest that IFN-gamma-induced activation of both fas and caspase-1 expression causes enhancement of hepatocyte apoptosis resulting in the development of hepatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Concanavalin A / immunology
  • Concanavalin A / toxicity*
  • Fas Ligand Protein
  • Hepatitis, Animal / chemically induced
  • Hepatitis, Animal / genetics
  • Hepatitis, Animal / immunology*
  • Hepatitis, Animal / pathology
  • Interferon-gamma / deficiency
  • Interferon-gamma / genetics
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Mice
  • Point Mutation
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • fas Receptor / genetics
  • fas Receptor / immunology*

Substances

  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • fas Receptor
  • Concanavalin A
  • Interferon-gamma