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Effects of TNFα and prostaglandin E 2 on the expression of MMPs in human periodontal ligament fibroblasts
Author(s) -
Nishikawa Masanori,
Yamaguchi Yoshinori,
Yoshitake Kazusada,
Saeki Yukikazu
Publication year - 2002
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1034/j.1600-0765.2002.00656.x
Subject(s) - matrix metalloproteinase , prostaglandin e2 , periodontal fiber , tumor necrosis factor alpha , endogeny , messenger rna , prostaglandin e , endocrinology , prostaglandin , medicine , periodontitis , chemistry , biology , biochemistry , dentistry , gene
Accumulating evidence indicates that TNFα plays an important role in the pathogenesis of periodontitis, but the effect of TNFα on the degradation of the periodontal ligament is not well understood. This study used reverse transcriptase‐PCR to investigate the effects of TNFα on matrix metalloproteinase (MMP) mRNA expression in human periodontal ligament fibroblasts. TNFα increased MMP‐1, MMP‐3 and MMP‐13 mRNA levels in both a time‐dependent (0–24 h) and a dose‐dependent (0.1–10 ng/ml) manner. TNFα also increased COX‐2 mRNA levels. Because elevation of COX‐2 mRNA levels enhances the production of prostaglandins, we therefore investigated whether endogenous prostaglandins are involved in the MMP mRNA expression that is enhanced by TNFα. Pre‐treatment with the selective COX‐2 inhibitor, NS‐398, increased MMP‐13 mRNA levels, while prostaglandin E 2 and dibutyryl cyclic AMP decreased MMP‐13 mRNA levels. Neither MMP‐1 nor MMP‐3 mRNA levels were affected by these chemicals. These findings indicate that prostaglandin E 2 has a lowering effect on TNFα‐enhanced MMP‐13 mRNA levels, and that this effect is dependent on cAMP. Our results suggest that TNFα participates in periodontal ligament destruction by stimulating the production of MMPs (MMP‐1, MMP‐3 andMMP‐13), while endogenous prostaglandin E 2 has a negative feedback role in TNFα‐enhanced MMP‐13 production.