REGULATION OF IL-1-INDUCED GINGIVAL COLLAGENASE GENE EXPRESSION BY ACTIVATOR PROTEIN-1 (c-FOS/c-JUN)

Matrix metalloproteinase-1 is probably involved in the progression of periodontal disease. The aim of this study was to investigate whether IL-1β stimulates the expression of the activator protein 1 (AP-1) transcription factor and, consequently, if the AP-1 transcription factor participates in the regulation of collagenase gene expression in human gingival fibroblast cells. In this study, we demonstrate that the concentration of the protein components of AP-1 transcription factor, c-Fos and c-Jun, is enhanced by IL-1β both at mRNA and protein levels, utilizing Northern blot analysis, electrophoretic mobility gel shift assay and Western blot analysis. The IL-1β stimulated the collagenase–CAT and AP-1–CAT activities in a dose dependent manner with respect to the amount of DNA used in transfections. Further, overexpression of c-Fos and c-Jun proteins revealed a dose-dependent transcriptional activation of the collagenase promoter. These findings, coupled with the existence of AP-1 consensus DNA binding sites on the collagenase gene promoter, show that regulation of collagenase gene expression by IL-1β involves the transcription factor AP-1 in gingival fibroblasts.