Involvement of tumor necrosis factor–related apoptosis-inducing ligand and tumor necrosis factor–related apoptosis-inducing ligand receptors in viral hepatic diseases
详细信息 查看全文
- 作者：Yukiko Saitou ; Katsuya Shiraki ; Hiroyuki Fuke ; Tomoko Inoue ; Kazumi Miyashita ; Yutaka Yamanaka ; Yumi Yamaguchi ; Norihik Yamamoto ; Keiichi Ito ; Kazushi Sugimoto ; Takeshi Nakano
- 关键词：TNF-related apoptosis-inducing ligand ; TRAIL ; TRAIL receptor 1 ; TRAIL-R1/DR4 ; TRAIL receptor 2 ; TRAIL-R2/DR5 ; Apoptosis ; Hepatitis ; HCV infection
- 刊名：Human Pathology
- 出版年：2005
- 出版时间：October 2005
- 年：2005
- 卷：36
- 期：10
- 页码：1066-1073
- 全文大小：371 K
文摘
Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) induces apoptosis in tumor cells, but not in most normal cells. The role of TRAIL in hepatic cell death and hepatic diseases is not well understood. The present study investigated the expression of TRAIL and TRAIL receptors (TRAIL-Rs) in patients with hepatitis C virus infection using immunohistochemistry and examined physiological roles under viral infection in the HepG2 cell line. Staining of TRAIL or TRAIL-Rs was prominent in the cytoplasm and membrane of hepatocytes in the periportal area. Some liver-infiltrating lymphocytes also displayed positive staining for TRAIL. Staining intensity was significantly increased with disease progression, particularly in the periportal area. AdCMVLacZ (Q-BIOgene, Carisbad, Calif) infection was also found to induce apoptosis in HepG2 cells and significantly augment TRAIL-induced apoptosis. Anti-TRAIL antibody significantly inhibited apoptosis induced by AdCMVLacZ infection. Flow cytometry analysis revealed that both TRAIL-R2 and TRAIL were up-regulated on the cell surface of HepG2 cells with AdCMVLacZ infection. Transforming growth factor–β1 also enhanced TRAIL expression in HepG2 cells. These results indicate that TRAIL/TRAIL-R apoptotic pathways play important roles in the hepatic cell death during viral infection.