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Regulation of Fas‐Mediated Apoptosis by NF‐κB Activity in Human Hepatocyte Derived Cell Lines
Author(s) -
Marusawa Hiroyuki,
Hijikata Makoto,
Watashi Koichi,
Chiba Tsutomu,
Shimotohno Kunitada
Publication year - 2001
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2001.tb02648.x
Subject(s) - apoptosis , biology , microbiology and biotechnology , nf κb , iκb kinase , cell culture , signal transduction , hepatocyte , programmed cell death , kinase , nfkb1 , iκbα , fas ligand , cancer research , transcription factor , gene , biochemistry , in vitro , genetics
Nuclear Factor‐κB (NF‐κB) is known to be one of the key regulators of genes involved in survival signaling. The purpose of this study is to investigate the role of NF‐κB activity in signaling events related to cell survival in hepatocytes, which has been supposed to be one of the most sensitive organs against Fas‐induced cytotoxicity. The functions of NF‐κB activity on Fas‐mediated apoptosis in different human cell lines were investigated by a magnetic concentration system for cells with exogenous protein production. We demonstrated that the activation of NF‐κB was triggered by anti‐Fas treatment in hepatocyte derived cell lines, HepG2 and Huh‐7 cells. Overexpression of kinase‐inactive NF‐κB‐inducing kinase (NIK) and IκB kinase (IKK) inhibited the activation of NF‐κB introduced by anti‐Fas treatment in these cells. Notably, inactivation of NF‐κB by the production of IκB‐α protein made these cells more susceptible to apoptosis induced by Fas stimulation. In contrast, transient expression of NIK showed a suppressive effect on Fas‐mediated apoptosis in the same cell lines. These findings suggest the involvement of NF‐κB in suppression of Fas‐mediated apoptosis in human hepatocyte derived cell lines, in which concomitant activation of this transcriptional factor was observed through the stimulation of Fas signaling.