Heme oxygenase is a positive acute-phase reactant in human Hep3B hepatoma cells.
The effects of human interleukin-6 (hIL-6), the major acute-phase inducer, on the level of the transcript of microsomal heme oxygenase (HO) were examined in a human hepatoma cell line, Hep3B. Messenger RNAs (mRNAs) encoding HO and haptoglobin (Hpt) increased after hIL-6 treatment in a time- and dose-dependent manner. hIL-6 had no effect on the induction of heat-shock protein 70 (hsp70) mRNA, suggesting that the induction of HO by hIL-6 is regulated by a different mechanism from that which mediates the heat-shock induction of this enzyme. The hIL-6-mediated induction of HO mRNA was completely abrogated by simultaneous treatment of cells with actinomycin D, but not with cycloheximide, suggesting that the induction occurs at the level of transcription. A nuclear factor was shown both in untreated, and in the hIL-6-treated Hep3B cells that binds specifically to the IL-6-responsive element (IL6-RE) of the human HO gene. These findings suggest that HO is a positive acute-phase reactant in this human liver-derived cell line, and that the nuclear factor specific to the IL6-RE may be involved in the activation of the HO gene after hIL-6 treatment.
Laboratory of Metabolism and Pharmacology, Rockefeller University Hospital, New York, NY 10021.
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Mitani
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Fujita
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Kappas
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Sassa
D000209:Acute-Phase Proteins / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction; D006360:Heat-Shock Proteins / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D009841:Oligonucleotides / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D006360:Heat-Shock Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D009841:Oligonucleotides; D012333:RNA, Messenger; D003609:Dactinomycin; D004247:DNA; D003513:Cycloheximide; D006419:Heme Oxygenase (Decyclizing)