肿瘤坏死因子与α干扰素联合通过增强结肠癌细胞中Fas的表达加速核因子κB介导的细胞凋亡。

TNF combined with IFN-alpha accelerates NF-kappaB-mediated apoptosis through enhancement of Fas expression in colon cancer cells.

作者信息

Kimura M, Haisa M, Uetsuka H, Takaoka M, Ohkawa T, Kawashima R, Yamatsuji T, Gunduz M, Kaneda Y, Tanaka N, Naomoto Y

机构信息

First Department of Surgery, Graduate School of Medicine and Dentistry, Okayama University, Japan.

出版信息

Cell Death Differ. 2003 Jun;10(6):718-28. doi: 10.1038/sj.cdd.4401219.

DOI:10.1038/sj.cdd.4401219

PMID:12761580

Abstract

Immunostaining and EMSA revealed that NF-kappaB was activated strongly by TNF/IFN-alpha compared to TNF alone in a human colon adenocarcinoma cell line, RPMI4788. Although inhibition of activated NF-kappaB, by using an NF-kappaB decoy, reduced cell viability after treatment with TNF only, NF-kappaB decoy resulted in recovery of cell viability after TNF/IFN-alpha treatment. Caspase-3 activity was increased in cells induced by TNF/IFN-alpha, while suppression of caspase-3 activity was observed in cells transfected with NF-kappaB decoy and then treated by TNF/IFN-alpha. On the other hand, Fas expression was strongly enhanced by TNF/IFN-alpha, and inhibition of TNF/IFN-alpha-induced NF-kappaB activation, by using NF-kappaB decoy, decreased Fas expression. Cell viability and caspase-3 activity decreased in cells treated with TNF/IFN-alpha and anti-FasL antibody. Taken together, our findings suggest that activated NF-kappaB induced by the crosstalk between TNF and IFN-alpha is a novel pro-apoptotic signal acting via enhancement of Fas expression.

摘要

免疫染色和电泳迁移率变动分析显示，在人结肠腺癌细胞系RPMI4788中，与单独使用TNF相比，TNF/IFN-α能强烈激活核因子κB（NF-κB）。尽管使用NF-κB诱饵抑制激活的NF-κB仅在TNF处理后降低了细胞活力，但NF-κB诱饵在TNF/IFN-α处理后导致细胞活力恢复。在TNF/IFN-α诱导的细胞中，半胱天冬酶-3（Caspase-3）活性增加，而在用NF-κB诱饵转染然后用TNF/IFN-α处理的细胞中观察到Caspase-3活性受到抑制。另一方面，TNF/IFN-α强烈增强Fas表达，使用NF-κB诱饵抑制TNF/IFN-α诱导的NF-κB激活会降低Fas表达。在用TNF/IFN-α和抗FasL抗体处理的细胞中，细胞活力和Caspase-3活性降低。综上所述，我们的研究结果表明，TNF和IFN-α之间的相互作用诱导的激活的NF-κB是一种通过增强Fas表达起作用的新型促凋亡信号。