title: Transcriptional downregulation of stromelysin by tetracycline.
abstract: 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.
authors.affiliation: Department of Immunopathology, Parke-Davis Pharmaceutical Research, Division of Warner Lambert Co., Ann Arbor, Michigan 48105, USA.
authors.forename: C
authors.initials: C
authors.lastname: Jonat
authors.forename: F Z
authors.initials: FZ
authors.lastname: Chung
authors.forename: V M
authors.initials: VM
authors.lastname: Baragi
mesh_terms: D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D017384:Sequence Deletion; D013752:Tetracycline / Q000494:pharmacology*; D018808:Transcription Factor AP-1; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D015500:Chloramphenicol O-Acetyltransferase; D019278:Matrix Metalloproteinase 3; D013752:Tetracycline