Jpn. J. Pharmacol. 79 (3), 289-294 (1999)

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

Toshihiro Okamoto (1), Yoshihisa Nakano (1), Tomio Yamakawa (1), Kaoru Hara (1), Ken-Ichi Yamamura (2) and Okio Hino (3)

(1) Research Laboratories, Nippon Chemiphar Co., Ltd., Saitama 341- 0005, Japan
(2) Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 862-0976, Japan
(3) Department of Experimental Pathology, Cancer Institute, Tokyo 170-8455, Japan

Abstract: Interferon-gamma (IFN-gamma) transgenic mice strongly express IFN-gamma in the liver and develop chronic hepatitis. Furthermore, hepatocyte apoptosis was shown by the TdT-mediated dUTP-biotin nick endlabeling method. In the present study, interleukin-1beta-converting enzyme (ICE) and CPP32-like protease activities in the liver of IFN-gamma 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-gamma 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-gamma transgenic mouse is associated with a decrease in ICE and induction of CPP32-like activity.

Keywords: Transgenic mouse, Liver, Chronic hepatitis, Interleukin-1beta-converting enzyme, CPP32

Copyrightę The Japanese Pharmacological Society 1999

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