Transcription from the stromelysin promoter is induced by interleukin-1 and repressed by dexamethasone.
The stromelysin gene encodes a potent tissue-degrading proteinase whose activity is important in tissue-remoldeling processes such as wound healing, the inflammatory reaction, rheumatoid arthritis, tumor invasion, and possibly embryonic development. In light of the ability of interleukin-1 to amplify, and ability of glucocorticoids to attenuate the inflammatory response, we tested interleukin-1 and dexamethasone for regulatory effects on stromelysin gene expression. We report that interleukin-1 induces the stromelysin gene, and dexamethasone diminishes the level of induction by interleukin-1, epidermal growth factor, phorbol ester, and cAMP elevation (elicited by cholera toxin). Similar responses are conferred upon a chloramphenicol acetyltransferase coding sequence by a 700-base pair stromelysin 5'-flanking fragment, implying transcription regulation by sequence elements in this region.
Frisch
S M
SM
Department of Pediatrics, Children's Hospital, Washington University School of Medicine, St. Louis, Missouri 63110.
Ruley
H E
HE
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics; D001483:Base Sequence; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology*; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000235:genetics*; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D011817:Rabbits; D012091:Repetitive Sequences, Nucleic Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014945:Wound Healing
D007375:Interleukin-1; D004815:Epidermal Growth Factor; D003907:Dexamethasone; D002772:Cholera Toxin; D000242:Cyclic AMP; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D013755:Tetradecanoylphorbol Acetate