MECHANISTIC FEATURES ASSOCIATED WITH INDUCTION OF METALLOPROTEINASES IN HUMAN GINGIVAL FIBROBLASTS BY INTERLEUKIN-1

Human gingival fibroblasts were treated with recombinant interleukin-1 (IL-1) to determine the effect of this stimulus on the relative expre ssion of collagenase (MMP-1), stromelysin (MMP-3) and plasminogen acti vator (PA) mRNA. The steady-stale mRNA levels for these genes were det ermined on Northern blots. IL-1 induced steady-state levels of these m RNAs to different extents. Nuclear run-on transcription studies showed that IL-1 induction of neutral metalloproteinase may be transcription ally regulated. Actinomycin D and protein kinase inhibitors decreased the mRNA production for all three metalloproteinases, whereas cyclohex imide decreased the production of collagenase and stromelysin mRNA. Pr otein kinase inhibitors (H7/H8) decreased production of the three mRNA s to different extents. This study demonstrates a potentially importan t role for IL-1 in the regulation of metalloproteinase expression in h uman gingival fibroblasts. The ability of IL-1 to induce the expressio n of stromelysin, collagenase and PA may define a pivotal role for thi s cytokine in the pathogenesis of periodontitis.