Cell death induction by CTL: perforin/granzyme B system dominantly acts for cell death induction in human hepatocellular carcinoma cells.

M. Hayashida, H. Kawano, T. Nakano, K. Shiraki, A. Suzuki
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引用次数: 13

Abstract

Cell death induction by cytotoxic T lymphocytes (CTLs) is an important thesis for the understanding of tumor immunotherapy. In the current study we investigated the molecular machinery of CTL-induced cell death in human hepatocellular carcinoma cell lines (HCC lines). CTLs prepared from human peripheral blood induced cell death in all tested HCC lines. As the CTL-induced death system, the effectiveness of Fas ligand/Fas and/or Perforin/Granzyme B systems has been suggested, whereas cell death induction by CTLs was shown independently on Fas expression in the current study. Using various tetrapeptide inhibitors for caspase and its associated factor, we additionally demonstrated that inhibitors for caspase 3 (Ac-DEVD-CHO) and caspase 8/granzyme B (Ac-IETD-CHO) suppressed CTL-induced cell death, but an inhibitor for Fas-activated serine proteinase, which acts for the caspase 3 activator, did not, suggesting that CTL-induced cell death was initiated by the Perforin/Granzyme B system, rather than the Fas ligand/Fas system. On the basis of our current results, we report here that the Perforin/Granzyme B system acts dominantly for the cell death induction of HCC lines.
CTL:穿孔素/颗粒酶B系统在诱导人肝癌细胞死亡中起主导作用。
细胞毒性T淋巴细胞(ctl)诱导细胞死亡是理解肿瘤免疫治疗的重要课题。在本研究中,我们研究了ctl诱导人肝癌细胞系(HCC细胞系)细胞死亡的分子机制。从人外周血制备的ctl可诱导所有HCC细胞系的细胞死亡。作为ctl诱导的死亡系统,Fas配体/Fas和/或Perforin/Granzyme B系统的有效性已被提出,而目前的研究显示ctl诱导细胞死亡独立于Fas表达。利用各种caspase及其相关因子的四肽抑制剂,我们还证明了caspase 3 (Ac-DEVD-CHO)和caspase 8/颗粒酶B (Ac-IETD-CHO)抑制剂抑制了ctl诱导的细胞死亡,但Fas激活的丝氨酸蛋白酶抑制剂(caspase 3激活剂)却没有,这表明ctl诱导的细胞死亡是由穿孔素/颗粒酶B系统启动的,而不是Fas配体/Fas系统。基于我们目前的结果,我们在此报告穿孔素/颗粒酶B系统在诱导HCC细胞系细胞死亡中起主要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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