PMID- 9481405 OWN - NLM STAT- MEDLINE DCOM- 19980316 LR - 20171207 IS - 0039-6060 (Print) IS - 0039-6060 (Linking) VI - 123 IP - 2 DP - 1998 Feb TI - Cytokine-mediated differential induction of hepatic activator protein-1 genes. PG - 191-8 AB - 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. FAU - Wang, S AU - Wang S AD - Department of Surgery, University of Texas Medical Branch, Galveston, 77555-0533, USA. FAU - Evers, B M AU - Evers BM LA - eng GR - P01 DK35608/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Surgery JT - Surgery JID - 0417347 RN - 0 (Cytokines) RN - 0 (Interleukin-6) RN - 0 (Proto-Oncogene Proteins c-jun) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factor AP-1) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Carcinoma, Hepatocellular/metabolism/pathology MH - Cytokines/*physiology MH - Gene Expression Regulation/*physiology MH - Humans MH - Interleukin-6/pharmacology MH - Liver/*physiology MH - Proto-Oncogene Proteins c-jun/genetics/metabolism MH - RNA, Messenger/metabolism MH - Transcription Factor AP-1/*genetics/metabolism MH - Tumor Cells, Cultured MH - Tumor Necrosis Factor-alpha/pharmacology EDAT- 1998/03/03 00:00 MHDA- 1998/03/03 00:01 CRDT- 1998/03/03 00:00 PHST- 1998/03/03 00:00 [pubmed] PHST- 1998/03/03 00:01 [medline] PHST- 1998/03/03 00:00 [entrez] AID - S0039-6060(98)70257-0 [pii] PST - ppublish SO - Surgery. 1998 Feb;123(2):191-8.