Transcriptional regulation of human stromelysin.

We have determined that human stromelysin mRNA can be induced by interleukin-1 beta (IL-1 beta) and that the induced mRNA levels can be suppressed by retinoic acid and dexamethasone (Saus, J., Quinones, S., Otani, Y., Nagase, H., Harris, E.D., Jr., and Kurkinen, M. (1988) J. Biol. Chem. 263, 6742-6745). Here we show, by nuclear run-on and transient gene expression analyses, that IL-1 beta induction is a promoter function and that dexamethasone suppresses IL-1 beta-induced gene activity. For transient gene expression assays, 1.3 kilobase pairs of the stromelysin promoter region (-1303 to -11 relative to the transcription start site) and shorter fragments thereof were cloned into a human growth hormone reporter vector. In transfected human fibroblast cultures all the constructs, with the exception of the one containing the shortest promoter fragment (-53 to -11), responded to IL-1 beta induction. Interestingly, the ability of IL-1 beta to induce human growth hormone expression decreased as the length of the promoter fragment was reduced. Dexamethasone treatment suppressed the induced human growth hormone levels by approximately 50% irrespective of the promoter length. These results suggest that the 1.3-kilobase pairs stromelysin promoter fragment contains DNA elements required for IL-1 beta induction and dexamethasone suppression.