Cell interactions between human gingival fibroblasts and monocytes stimulate the production of matrix metalloproteinase-1 in gingival fibroblasts

Background: Matrix metalloproteinase-1 (MMP-1) plays an important role in inflammatory diseases including periodontitis, which is characterized by tissue destruction and dense infiltration of mononuclear cells. Objectives: The aim of this study was to investigate the effect of cell interactions between human gingival fibroblasts and human monocytes on the production of MMP-1 in a coculture model. Methods: The fibroblasts were cultured in either cell-to-cell contact with monocytes or in separated cocultures using a microporous membrane to prevent cell-to-cell contact. The mRNA expression of MMP-1 was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) and the protein levels of MMP-1 in the cell medium were measured using enzyme-linked immunosorbent assay (ELISA). Results: Coculturing gingival fibroblasts with monocytes in cell-to-cell contact increased the mRNA expression of MMP-1 in both fibroblasts and monocytes. The protein levels of MMP-1 increased in the culture media of the cocultures and correlated to the number of fibroblasts as well as to the number of monocytes. When fibroblasts were cultured with monocytes in separated cocultures, the mRNA expression and protein level of MMP-1 increased in the fibroblasts. In addition, treatment of fibroblasts with conditioned medium from monocytes also stimulated the production of MMP-1 in the fibroblasts. Moreover, the levels of the MMP-1 inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), increased in cocultures with cell-to-cell contact, but not in fibroblasts of separated cocultures. The glucocorticoid dexamethasone and the tetracycline doxycycline reduced the enhanced level of MMP-1 in the cocultures with cell-to-cell contact. Conclusion: The current study demonstrates that monocytes stimulate the production of MMP-1 in gingival fibroblasts by cell interactions which may, contribute to the maintenance of MMP-mediated tissue destruction in periodontitis.