Chronic hepatitis in interferon-gamma transgenic mice is associated with elevated CPP32-like activity and...

Area of Science:

• Hepatology
• Immunology
• Molecular Biology

Background:

• Interferon-gamma (IFN-gamma) transgenic mice exhibit liver expression of IFN-gamma, leading to chronic hepatitis.
• Hepatocyte apoptosis is a key feature of liver damage in these mice.

Purpose of the Study:

• To investigate the roles of interleukin-1beta-converting enzyme (ICE) and CPP32-like protease activity in the pathogenesis of chronic hepatitis in IFN-gamma transgenic mice.
• To elucidate the specific protease activities contributing to liver injury.

Main Methods:

• Measurement of ICE and CPP32-like protease activities in liver cytosol using synthetic substrates (Ac-YVAD-MCA and Ac-DEVD-MCA).
• Assessment of plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities.
• Inhibition studies using Ac-YVAD-CHO (ICE inhibitor) and a CPP32 inhibitor on liver cell cytosol.

Main Results:

• Significantly elevated plasma AST and ALT activities, indicative of liver damage.
• Significantly reduced ICE activity and significantly induced CPP32-like protease activity in the liver of IFN-gamma transgenic mice.
• ICE inhibition did not affect CPP32 activity, whereas CPP32 inhibition did, suggesting distinct roles.

Conclusions:

• Chronic hepatitis in IFN-gamma transgenic mice is characterized by a decrease in ICE activity.
• The induction of CPP32-like protease activity is associated with liver injury in this model.
• These findings highlight the differential involvement of caspases in IFN-gamma-mediated liver disease.