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Cytokine-mediated differential induction of hepatic activator protein-1 genes
1Department of Surgery, University of Texas Medical Branch, Galveston, 77555-0533, USA.
Background:
Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) increase the synthesis of hepatic acute-phase proteins; these effects appear mediated by activation of transcription factors. The purpose of this study was to determine the effects of TNF-alpha and IL-6 on expression of the jun family of activator protein-1 (AP-1) transcription factors with the human hepatoma cell line HepG2, a well-characterized model of the hepatic acute-phase response.
Methods:
HepG2 cells, treated with either TNF-alpha (100 ng/ml) or IL-6 (10 ng/ml), were extracted for RNA and protein (total and nuclear) and analyzed.
Results:
TNF-alpha increased c-jun and junD mRNA and c-Jun and JunD protein levels, as well as AP-1 binding activity. IL-6 increased c-jun mRNA, c-Jun protein, and AP-1 binding activity but did not affect either junD or junB expression.
Conclusions:
TNF-alpha and IL-6 induce a differential pattern of AP-1 expression in HepG2 cells; TNF-alpha increases both c-Jun and JunD, whereas IL-6 stimulates only c-Jun. Neither TNF-alpha nor IL-6 stimulates JunB. Multiple cytokines, released during stress, may act in concert to stimulate the AP-1 proteins, which ultimately culminate in the downstream synthesis of a variety of acute-phase proteins.