The type II hemopexin interleukin-6 response element predominates the transcriptional regulation of the hemopexin acute phase responsiveness.
Hemopexin (Hx) is induced during the acute phase response (APR) by the cytokine interleukin (IL)-6. A type II IL-6 response element (RE) of the Hx gene has been characterized recently (J. Biol. Chem. (1994); 269, 12654-12661). To assess Hx gene regulation by other agents, various cytokines and growth factors were tested for their ability to induce Hx in rat hepatoma H-35 cells. IL-6-type cytokines, IL-1 beta and TNF-alpha, in contrast to transforming growth factor-beta (TGF-beta), hepatocyte growth factor and insulin significantly increased Hx gene expression. Chloramphenicol acetyltransferase (CAT) activity in H-35 cells transfected with constructs that contained the 5'-flanking Hx promoter region or multiple copies of the Hx IL-6-RE fused to the CAT gene was upregulated only by IL-6-type cytokines, although to varying degrees. These data indicate that signal transduction pathways mediated by IL-6-type cytokines but not those by IL-1 beta and TNF-alpha converge on the common Hx IL-6-RE.
Department of Pediatrics, Cornell University Medical College, New York, NY 10021.
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Immenschuh
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Satoh
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Muller-Eberhard
D000818:Animals; D002999:Clone Cells; D016207:Cytokines / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006133:Growth Substances / Q000494:pharmacology*; D006466:Hemopexin / Q000096:biosynthesis*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D016207:Cytokines; D006133:Growth Substances; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003907:Dexamethasone; D006466:Hemopexin