MMP-3 Regulation by IL-1b in Human Hereditary Gingival Fibromatosis Fibroblasts

MMP-3 Regulation by IL-1b in Human Hereditary Gingival Fibromatosis Fibroblasts.  W. Hammontree*, D. Tipton, and M. Dabbous.  Dental Research Center, College of Dentistry, University of Tennessee Health Science Center, Memphis, TN Hereditary gingival fibromatosis (HGF), a fibrotic gingival enlargement, usually occurs upon tooth eruption.  HGF fibroblasts produce more collagen, fibronectin, and the fibrogenic molecule TGFb than normal gingival (GN) fibroblasts.  Matrix metalloproteinases (MMPs) degrade extracellular matrix molecules; previous work suggested autocrine TGFb effects on MMP expression by HGF fibroblasts. MMP-3 is upregulated in GN fibroblasts by IL-1b and appears to play a significant role in periodontal degradation, but its production, regulation by IL-1b, and role in HGF are not clear. Objectives: determine constitutive and IL-b-stimulated MMP-3 production in matched GN and HGF fibroblasts. Methods: Fibroblasts were incubated ± IL-1b (1x10^-10M) for 6d. Total MMP-3 [active, proenzyme, and complexed with tissue inhibitor of metalloproteinases (TIMP)] and inactive MMP-3/TIMP-1 complex in culture supernatants were measured by specific ELISAs. Data were analyzed using ANOVA. Results: All fibroblasts constitutively produced MMP-3. HGF fibroblasts generally produced the same or more total MMP-3 than GN cells (p≤0.04). IL-1b increased total MMP-3 production in all cell lines, but generally to a lesser extent in HGF fibroblasts (p≤0.04). Constitutively, the percent of total MMP-3 complexed with TIMP-1 was similar in the two cell types, but when stimulated with IL-1b these levels were generally higher in HGF compared to GN (p≤0.03). Conclusion: The data suggest that under inflammatory conditions (i.e. tissue damage associated with tooth eruption) decreased magnitude of total MMP-3 production by HGF fibroblasts and comparatively greater levels of inactive MMP-3/TIMP-1 complex may contribute to matrix accumulation in HGF. (Supported by UT College of Dentistry Alumni Endowment Fund).