Inflammation Research

, Volume 46, Issue 8, pp 320–323

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

  • S. Takahashi
  • T. Inoue
  • M. Higaki
  • Y. Mizushima

DOI: 10.1007/s000110050194

Cite this article as:
Takahashi, S., Inoue, T., Higaki, M. et al. Inflamm. res. (1997) 46: 320. doi:10.1007/s000110050194

Abstract.

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) (100 ng/ml) and/or indomethacin (0.1, 1, 10 μM) and diclofenac (0.1, 1, 10 μM) and/or prostaglandin E2 (PGE2) (1, 10 μM) for 72 h.¶Methods: The amounts of TIMP-1, proMMP-1 and PGE2 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 PGE2 significantly suppresses indomethacin- and diclofenac-enhanced TIMP-1 and proMMP-1 production.¶Conclusion: PGE2 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 PGE2 production in inflammation.

Key words: TIMP-1 — MMP-1 — Indomethacin — Diclofenac

Copyright information

© Birkhäuser Verlag, Basel, 1997

Authors and Affiliations

  • S. Takahashi
    • 1
  • T. Inoue
    • 1
  • M. Higaki
    • 1
  • Y. Mizushima
    • 1
  1. 1.Division of Rheumatology, Institute of Medical Science, St. Marianna University, School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki-shi, Kanagawa 216, JapanJP