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.