Effects of recombinant interleukin-1 beta on decorin gene expression in human periodontal ligament fibroblast and its possible transcriptional regulation.

Interleukin-1 beta (IL-1 beta) is a potent regulator of osteoprogenitor cells and fibroblasts, and is believed to be responsible for the bone loss and connective tissue breakdown that occurs in periodontitis. Decorin, a major small proteoglycan in the periodontium, has been shown as an important mediator of the organization of the pericellular and extracellular matrix. Since the HPLF play a significant role in the regulation of extracellular matrix metabolism, it was important to clarify the causal relationship between cytokines, HPLF and proteoglycans. We investigated the effect of IL-1 beta on decorin gene expression and its functional regulation to elucidate the intracellular mechanism mediating the action of IL-1 beta. Quiescently confluent HPLF cultures were incubated for different treatment periods with various concentrations of IL-1 beta and/or 10(-4) M cycloheximide (Cx) in culture medium supplemented with 1% charcoal-stripped serum for different treatment periods. Northern hybridization analyses, using decorin cDNA probe, showed that IL-1 beta increased the abundance of decorin mRNA in both a dose- and time-dependent manner. Most of the stimulation was blocked by Cx, indicating that the regulation of decorin gene expression by IL-1 beta may be via an indirect pathway, requiring new protein synthesis which regulates the promoter. Gel mobility shift analyses detected the specific DNA binding activity of a nuclear extract of AP-1, but not NF-kappa B, that could bind to the recognition site of decorin gene promoter fragments with the increased abundance in IL-1 beta treatment groups. These results suggest that the increased transcription of decorin gene by HPLF in the presence of IL-1 beta is mediated at least in part through the interaction of AP-1 with the decorin gene promoter.