Interleukin-1 (IL-1) the production of metalloproteinases [e.g., collagenase and stromelysin (proteoglycanase)] in gingival fibroblasts and thereby has been linked to gingival soft tissue destruction associated with periodontitis. The intracellular biochemical events that link IL-1 gingival fibroblast receptor activation to metalloproteinase gene activation are poorly understood. It is likely that a number of proteins e.g. pre-transcription/post-transcription regulatory proteins, protease inhibitors, and various other unidentified factors play key roles in the modulation of these metalloproteinases. Recent studies of gingival fibroblasts in culture have provided new insights into the molecular events associated with IL-1 inducible transcription factors could play key roles in the modulation of collagenase gene expression. The present proposal involves a series of experiments designed to study the specific role of Stat3 transcription factor in the regulation of gingival collagenase gene expression by IL-1. The proposed in-vitro studies offer a model system to provide fundamental molecular information on the activation of the collagenase gene by IL-1 in human gingival fibroblasts, subsequent to the onset of periodontitis. This can elucidate events that could be involved in the pathogenesis. Consequently, an important implication of the present proposal is that these modulators of gingival collagenase gene expression could be useful in future in vivo clinical studies.
