Cyclooxygenase inhibitors enhance the production of tissue inhibitor-1 of metalloproteinases (TIMP-1) and pro-matrix metalloproteinase 1 (proMMP-1) in human rheumatoid synovial fibroblasts

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作者：

S Takahashi，T Inoue，M Higaki，Y Mizushima

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摘要：

Objective and Design: We investigated the influence of cyclooxygenase inhibitors against the production of tissue inhibitor-1 of metalloproteinases (TIMP-1) and pro-matrix metalloproteinase 1 (proMMP-1) in rheumatoid arthritis (RA) synoviocytes. Material: Synovial fibroblasts from RA patients were used. Treatment: The cells were treated with recombinant human interleukin 1β (rhIL-1β) (100ng/ml) and/or indomethacin (0.1, 1, 10μM) and diclofenac (0.1, 1, 10μM) and/or prostaglandin E 2 (PGE 2 ) (1, 10μM) for 72h. Methods: The amounts of TIMP-1, proMMP-1 and PGE 2 was measured by enzyme linked immunosorbent assay (ELISA). Statistical significance was tested with Student's t-test and Dunnett test. Results: RhIL-1β augments the production of TIMP-1 and proMMP-1 in synovial fibroblasts from RA patients, and this IL-1-induced production of TIMP-1 and proMMP-1 was further enhanced by treatment with the cyclooxygenase inhibitors, indomethacin and diclofenac. Exogenous PGE 2 significantly suppresses indomethacin- and diclofenac-enhanced TIMP-1 and proMMP-1 production. Conclusion: PGE 2 down-regulates the production of TIMP-1 and proMMP-1 in RA synoviocytes, and cyclooxygenase inhibitors regulate the production of TIMP-1 and proMMP-1 through the inhibition of PGE 2 production in inflammation.

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关键词：

TIMP-1 — MMP-1 — Indomethacin — Diclofenac

DOI：

10.1007/s000110050194

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年份：

1997