Transcriptional downregulation of stromelysin by tetracycline

We investigated the role of tetracycline in the transcriptional regulation of matrix metalloproteinases. Using interleukin-1beta (IL-1) induced stromelysin as a model system, we describe the repression of the endogenous stromelysin RNA accumulation, as well as the transcriptional inhibition of various stromelysin promoter/chloramphenicol-acetyltransferase constructs in transient transfection assays. The inhibition occurred in a dose-dependent fashion, with an IC50 of about 1 microM. Our results suggest that the transcriptional inhibition by tetracycline is not due to a block of activity of the activating protein complex 1 (AP-1) but is mediated by sequences upstream of the AP-1 binding site.