Signal pathways involved in the production of MMP‐1 and MMP‐3 in human gingival fibroblasts

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Abstract
Periodontitis is associated with enhanced production of cytokines, prostaglandins and matrix metalloproteinases (MMPs). The aim of this study was to investigate the production and regulation of MMP‐1 and MMP‐3 in human gingival fibroblasts challenged with the cytokines interleukin‐1β (IL‐1β), tumor necrosis factor α (TNFα) or epidermal growth factor (EGF). The results showed that gingival fibroblasts constitutively produce MMP‐1 and MMP‐3, and that the cytokines IL‐1β, TNFα and EGF increase both MMP‐1 and MMP‐3 production in gingival fibroblasts. The upregulation by the cytokines was apparent at 8 h of incubation and increased thereafter continuously during 48 h of incubation. The upregulation of MMPs, induced by IL‐1β or TNFα, was reduced by the cyxlooxygenase‐2 (COX‐2) inhibitor NS‐398, the p38 MAP‐kinase inhibitor SB 203580, and the tyrosine kinase inhibitor herbimycin A. In addition, MMP‐1 and MMP‐3 production, induced by IL‐1β, TNFα or EGF, was strongly reduced by the presence of the glucocorticoid dexamethasone. Our findings demonstrate that the cytokines IL‐1β, TNFα and EGF, respectively, enhance both MMP‐1 and MMP‐3 production in human gingival fibroblasts, and that the signal pathways COX‐2, MAP‐kinases and tyrosine kinases are partly involved in the production of MMPs.

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