Concomitant gene expressions of perforin and Fas-ligand in the liver of chronic hepatitis C

慢性丙型肝炎肝脏中穿孔素和Fas配体的伴随基因表达

• 批准号: 07670573
• 负责人: TANAKA Yujiro
• 金额: $ 1.47万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670573/
• 关键词: HCV; cytotoxic T lymphocyte; apoptosis; necrosis; PCR

In chronic hepatitis C,the involvement of cytotoxic T cells (CTLs) has been suspected mainly on the basis of histological findings of the liver. CTLs induce their target-cell death through perforin and/or Fas-ligand-Fas dependent pathways. The purpose of this study is to clarify the mechanism of CTL-mediated cytotoxicity in chronic hepatitis C by assessing the two pathways. The liver biopsy specimens were obtained from eight cases of chronic hepatitis C and, for comparison, four cases free of hepatitis C virus (HCV) after interferon treatment. Hepatic messenger RNAs of perforin, Fas-ligand, and CD8 were reverse transcribed, amplified inthe presence of their DNA competitors by polymerase chain reaction, and quantitated on an DNA Sequencer. Both hepatic mRNA levels of perforin and Fas-ligand, which were corrected by the level of CD8 mRNA,were elevated in chronic HCV infection, whereas they were nearly undetectable in the cases free of HCV.Among the cases of HCV infection, the ratio of Fas-ligand-mRNA/perforin-mRNA was significantly correlated with serum alanine aminotransferase levels (r=0.94). These results suggest the involvement of CTL-mediated cytotoxicity via both perforin and Fas-dependent pathways and the variable predominance of the dual pathways in chronic hepatitis C.

在慢性丙型肝炎中，细胞毒性T细胞（ctl）的参与主要是基于肝脏的组织学发现。ctl通过穿孔素和/或fas -配体- fas依赖途径诱导其靶细胞死亡。本研究的目的是通过评估这两种途径来阐明ctl介导的慢性丙型肝炎细胞毒性的机制。从8例慢性丙型肝炎患者和4例经干扰素治疗后无丙型肝炎病毒（HCV）的患者中获得肝活检标本进行比较。肝穿孔素、fas配体和CD8的信使rna被逆转录，在它们的DNA竞争对手存在的情况下通过聚合酶链反应扩增，并在DNA测序仪上定量。肝脏穿孔素和fas配体的mRNA水平在慢性HCV感染中升高，而在无HCV感染的病例中几乎检测不到。在HCV感染病例中，fas -配体- mrna /perforin-mRNA比值与血清丙氨酸转氨酶水平显著相关（r=0.94）。这些结果表明，慢性丙型肝炎通过穿孔素和fas依赖途径参与ctl介导的细胞毒性，并在双重途径中占可变优势。

项目成果

Yujiro Tanaka: "Concomitant gene expressions of perforin and Fas-ligand in the liver of chrcnic hepatitis C" Hepatology. (in press).

Yujiro Tanaka：“慢性丙型肝炎肝脏中穿孔素和 Fas 配体的伴随基因表达”肝病学。

Yujiro Tanaka, Fumihiko Kusano, Kozo Ishidate, Takatoshi Sakamoto, Nobuyuki Enomoto, Fumiaki Marumo, Chifumi Sato: "Concomitant gene expressions perforin and Fas-ligand in the liver of chronic hepatitis C Hepatology" (in press).

Yujiro Tanaka、Fumihiko Kusano、Kozo Ishidate、Takatoshi Sakamoto、Nobuyuki Enomoto、Fumiaki Marumo、Chifumi Sato：“慢性丙型肝炎肝病学肝脏中穿孔素和 Fas 配体的伴随基因表达”（出版中）。

Yujiro Tanaka. et.al.: "Con Comitant gene expressions of perforin and Fas figand in the liver of chronic hepatitis C" Hepatology. (in press).

田中雄二郎.