Zheng Shi-Jun, Wang Pu, Tsabary Galit, Chen Youhai H
Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
J Clin Invest. 2004 Jan;113(1):58-64. doi: 10.1172/JCI19255.
The TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis of tumor cells but not most normal cells. Its role in hepatic cell death and hepatic diseases is not clear. In vitro studies suggest that murine hepatocytes are not sensitive to TRAIL-induced apoptosis, indicating that TRAIL may not mediate hepatic cell death. Using two experimental models of hepatitis, we found that hepatic cell death in vivo was dramatically reduced in TRAIL-deficient mice and mice treated with a blocking TRAIL receptor. Although both TRAIL and its death receptor 5 were constitutively expressed in the liver, TRAIL expression by immune cells alone was sufficient to restore the sensitivity of TRAIL-deficient mice to hepatitis. Thus, TRAIL plays a crucial role in hepatic cell death and hepatic inflammation.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）可诱导肿瘤细胞凋亡，但对大多数正常细胞无此作用。其在肝细胞死亡及肝脏疾病中的作用尚不清楚。体外研究表明，小鼠肝细胞对TRAIL诱导的凋亡不敏感，这表明TRAIL可能不介导肝细胞死亡。利用两种肝炎实验模型，我们发现，在TRAIL缺陷小鼠和用TRAIL受体阻断剂处理的小鼠中，体内肝细胞死亡显著减少。尽管TRAIL及其死亡受体5在肝脏中均有组成性表达，但仅免疫细胞表达的TRAIL就足以恢复TRAIL缺陷小鼠对肝炎的敏感性。因此，TRAIL在肝细胞死亡和肝脏炎症中起关键作用。
