Chronic Hepatitis in Interferon-γ Transgenic Mice Is Associated With Elevated CPP32-Like Activity and Interleukin-1β-Converting Enzyme Activity Suppression

Abstract

Interferon-γ (IFN-γ) transgenic mice strongly express IFN-γ in the liver and develop chronic hepatitis. Furthermore, hepatocyte apoptosis was shown by the TdT-mediated dUTP-biotin nick endlabel- ing method. In the present study, interleukin-1β-converting enzyme (ICE) and CPP32-like protease activ- ities in the liver of IFN-γ transgenic mice were measured, using the synthetic substrates Ac-YVAD-MCA and Ac-DEVD-MCA. Plasma aspartate aminotransferase and alanine aminotransferase activities as well as CPP32-like activity were significantly elevated, while ICE activity was significantly reduced. The addition of the ICE inhibitor Ac-YVAD-CHO to IFN-γ transgenic mouse liver cell cytosol had no effect on the CPP32 activity, in contrast to a CPP32 inhibitor. The present results indicate that chronic hepatitis in the IFN-γ transgenic mouse is associated with a decrease in ICE and induction of CPP32-like activity.