The protective effect of cyclosporine A on anti-Fas antibody-induced hepatitis in mice.
The effect of cyclosporine A (CsA) on anti-Fas antibody-induced hepatitis was studied. The administration of anti-Fas antibody (250 microg/kg) to mice elevated plasma alanine aminotransferase (ALT) activity at 3 hr. This anti-Fas antibody-induced elevation of ALT was inhibited by treatment with CsA (10, 30 and 100 mg/kg) in a dose-dependent manner. Anti-Fas antibody administration elevated CPP32-like protease activity at 3 hr in mouse liver, and this elevation of CPP32-like activity was inhibited by treatment with CsA. The present results show that CsA treatment inhibits the anti-Fas antibody-induced apoptotic process of hepatitis, at least in part, by affecting a reaction upstream of CPP32-like protease activation.
Okamoto
T
T
Research Laboratories, Nippon Chemiphar Co., Ltd., Misato, Saitama, Japan.
Hitomi
Y
Y
Hara
A
A
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000517:prevention & control*; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D019014:fas Receptor; D016572:Cyclosporine; D000410:Alanine Transaminase; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases