Caspase-1 is not involved in experimental hepatitis in mouse

FEBS Lett. 1999 Feb 19;445(1):115-8. doi: 10.1016/s0014-5793(99)00109-x.

Abstract

Experimental hepatitis induced by tumor necrosis factor in D-(+)-galactosamine-sensitized mice or by an agonistic anti-Fas antibody in normal mice is accompanied by dramatic apoptosis of hepatocytes. Apoptosis is the final result of activation of a cascade of caspases. We used caspase-1-/- mice, generated by gene targeting, to study the role of this protease in TNF- and anti-Fas-induced lethal hepatitis. We found that mutant mice exhibited the typical caspase-1-/- phenotype, since they resisted to a lethal injection of LPS and released no interleukin-1beta in the circulation, in contrast to wild-type littermates. When caspase-1-/- mice were challenged with different doses of tumor necrosis factor/D-(+)-galactosamine or with anti-Fas, no increased survival was observed compared with control mice. Furthermore, apoptosis in the livers of these mice and serum levels of alanine aminotransferase were not reduced. These data indicate that caspase-1 deficiency does not lead to reduced apoptosis in these models, either because caspase-1 is irrelevant in this model or because of functional redundancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 1 / genetics
  • Caspase 1 / physiology*
  • DNA Fragmentation
  • Disease Models, Animal
  • Female
  • Galactosamine / metabolism
  • Galactosamine / pharmacology
  • Hepatitis / etiology*
  • Interleukin-1 / biosynthesis
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Knockout
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • fas Receptor / immunology
  • fas Receptor / metabolism

Substances

  • Interleukin-1
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Galactosamine
  • Caspase 1