Induction of dental pulp fibroblast matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 gene expression by interleukin-1 alpha andtumor necrosis factor-alpha through a prostaglandin-dependent pathway

Matrix metalloproteinase-l (MMP-1) and tissue inhibitor of metalloproteinas e-l (TIMP-1) are involved in the degradation of extracellular matrix in man y inflammatory diseases. Little is known regarding the expression of these mediators in dental pulp fibroblasts. The effects of proinflammatory cytoki nes (interleukin (IL)-1 alpha and tumor necrosis factor-alpha (TNF-alpha)) and prostaglandin E-2 (PGE(2)) on pulp fibroblast MMP-1 and TIMP-1 gene exp ression were investigated. Northern hybridization showed that IL-1 alpha an d TNF-alpha induced significant MMP-1 gene expression, with only little eff ect on TIMP-1 gene. Exogenous PGE(2), however, upregulated TIMP-1 mRNA synt hesis but not MMP-1. Concomitant addition of IL-1 alpha and PGE(2) or TNf-a lpha and PGE(2) suppressed MMP-1 mRNA production, compared with the groups treated with IL-1 alpha or TNF-alpha alone. In contrast, PGE(2) enhanced th e upregulatory effects of TIMP-1 mRNA by IL-1 alpha or TNF-(2). Furthermore , cytokine stimulation of MMP-1 and TIMP-1 gene expressions can be enhanced or blocked by indomethacin, respectively, and reversed by exogenous PGE(2) . These results suggested that cytokine-stimulated MMP-1 and TIMP-1 gene ex pression in dental pulp fibroblasts was mediated, at least in part, by a pr ostaglandin-dependent pathway. The differential regulation of IL-1 alpha or TNF-alpha -induced MMP-1 and TIMP-1 mRNA synthesis, as well as the direct upregulation of TIMP-1 gene expression by PGE(2), also implied that prostag landin may serve as a protective mechanism from excessive tissue breakdown during pulpitis.