Interleukin 6 induces a liver-specific nuclear protein that binds to the promoter of acute-phase genes.
Interleukin 6 (IL-6) is responsible for a variety of biological effects related to the activation of defenses against infection or inflammation, including the immune response and the acute-phase reaction. Its mechanism of action is unknown. It has recently been shown to induce transcription of several genes encoding acute-phase proteins. Here we describe the identification of an IL-6 responsive element (IL-6RE) present in the promoter of the human hemopexin gene. This element is necessary and sufficient for the IL-6-dependent activation of transcription. The IL-6 effect does not require de novo protein synthesis. A liver-specific nuclear protein (IL-6DBP) binds to the hemopexin IL-6RE as well as to similar sequences on the promoter of other acute-phase genes. IL-6DBP DNA binding activity is induced by IL-6 via a posttranslational mechanism.
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European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.
Cortese
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D000209:Acute-Phase Proteins / Q000235:genetics*; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D005796:Genes; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008113:Liver Neoplasms; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000378:metabolism; D015345:Oligonucleotide Probes; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins; D014162:Transfection
D000209:Acute-Phase Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D011994:Recombinant Proteins; D015500:Chloramphenicol O-Acetyltransferase