Differential regulation of rat T-kininogen by tumor necrosis factor and interleukin-6.
Rat T-kininogen (T-KG), a cysteine protease inhibitor, is an acute phase reactant which is induced to high levels in response to inflammation. Both hormones and cytokines participate in this regulation. To investigate the cis-acting elements responsible for the induction of gene expression, various 5'-fragments of the rat T-KG gene were fused to a chloramphenicol acetyltransferase marker gene. These constructs were transfected into a rat hepatoma cell line which was then treated with tumor necrosis factor or interleukin-6 or both cytokines. Expression of the chloramphenicol acetyltransferase gene was induced with interleukin-6 treatment, but suppressed by tumor necrosis factor. The 5'-region of the T-KG gene responsible for conferring both of these effects was localized between nucleotides -404 to -210 upstream of the transcription start site. Fragments containing this region were found to be effective in either orientation, and could also regulate a heterologous promoter.
Anderson
K P
KP
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Ohio 45267-0524.
Lingrel
J B
JB
D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D007704:Kininogens / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000473:pathology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000187:drug effects; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000209:Acute-Phase Proteins; D015850:Interleukin-6; D007704:Kininogens; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha