Caspase‐1 is not involved in experimental hepatitis in mouse

FEBS Letters

Libert, Claude¹  van Molle, Wim¹  Brouckaert, Peter¹ 

[1] Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and University of Ghent, K.L. Ledeganckstraat 35, B-9000 Ghent, Belgium

关键词: Apoptosis;    Caspase;    Hepatitis;    Tumor necrosis factor;   

DOI  :  10.1016/S0014-5793(99)00109-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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-1β 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.

【 授权许可】

Unknown