Interleukin 1β protects mice from Fas-mediated hepatocyte apoptosis and death

作     者：Takehara, T Hayashi, N Tatsumi, T Kanto, T Mita, E Sasaki, Y Kasahara, A Hori, M 

作者机构：Osaka Univ Grad Sch Med Dept Mol Therapeut Osaka 5650871 Japan Osaka Univ Grad Sch Med Dept Internal Med & Therapeut Osaka 5650871 Japan Osaka Univ Grad Sch Med Dept Gen Med Osaka 5650871 Japan 

出 版 物：《GASTROENTEROLOGY》 (胃肠病学)

年 卷 期：1999年第117卷第3期

页      面：661-668页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Ministry of Education  Culture  Sports  Science and Technology  MEXT 

主　　题：丙氨酸转氨酶/血液 细胞凋亡/药物作用 细胞凋亡/生理学 半胱氨酸天冬氨酸蛋白酶3 半胱氨酸天冬氨酸蛋白酶/代谢 细胞死亡/药物作用 细胞死亡/生理学 DNA碎片裂 酶前体/代谢 流式细胞术 白细胞介素1/药理学 白细胞介素1/生理学 肝/细胞学 肝/药物作用 肝/代谢 小鼠 近交BALBC 动物 女(雌)性 小鼠 

摘      要：Background & Aims: Fas-mediated apoptosis is one of the major death processes of hepatocytes in liver diseases. The aim of this study was to determine whether interleukin (IL)-1 beta regulates the Fas-mediated apoptotic process of differentiated hepatocytes in vivo. Methods: IL-1 beta was injected into Balb/cA mice 5 hours before lethal challenge with agonistic anti-fas administration. Survival and hepatocyte apoptotic process of these mice were examined. Results: IL-1 beta pretreatment prolonged animal survival in a dose-dependent manner, and 500 ng of IL-1 beta completely protected mice from lethality. Both serum alanine aminotransferase value and hepatic DNA fragmentation were significantly suppressed by IL-1 beta pretreatment. IL-1 beta affected neither hepatic distribution of anti-fas antibody nor Fas expression levels on hepatocytes but significantly suppressed Fas-induced activation of hepatic caspase 3-like protease. Suppression of Fas-induced activation of the caspase by IL-1 beta was diminished by coadministration with D-galactosamine and reversed by coinjection with an excess amount of uridine. Conclusions: These results suggest that IL-1 beta suppresses Fas-mediated hepatocyte apoptosis by inducing molecule(s) that suppress the apoptosis control machinery upstream of caspase 3. This observation raises the possibility that IL-1 beta acts as a negative regulator of Fas-mediated hepatocyte apoptosis during liver injury.