ISSN:
1420-908X
Keywords:
Key words: Aceclofenac — 4′-Hydroxy aceclofenac — Pro-matrix metalloproteinase 1 — Pro-matrix metalloproteinase 3 — Rheumatoid synovial cell
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract. Objective and Design: We examined the effects of aceclofenac and its metabolites on the production of pro-collagenase-1/pro-matrix metalloproteinase-1 (proMMP-1), pro-gelatinase A/proMMP-2, pro-stromelysin-1/proMMP-3 and tissue inhibitor of metalloproteinases-1 (TIMP-1) by rheumatoid synovial cells.¶Materials: Synovial cells were obtained from patients with rheumatoid arthritis.¶Treatment: Cultures of confluent cells were treated with interleukin-1β (IL-1β)(1 ng/ml) and/or test drugs (0.3-30 μM) for 48 h.¶Methods: Production of proMMPs and TIMP-1 was monitored by Western blotting or gelatin zymography. Prostaglandin E2 (PGE2) was measured by an enzyme immunoassay.¶Results: 4′-Hydroxy aceclofenac, a major metabolite of aceclofenac, down-regulated both basal and IL-1β-induced production of proMMP-1 and proMMP-3 at a concentration sufficient to suppress PGE2 production without modulating proMMP-2 or TIMP-1, whereas aceclofenac itself had no marked effect on the production of proMMPs.¶Conclusions: Down-regulation of proMMP-1 and proMMP-3 production by 4′-hydroxy aceclofenac may contribute to the therapeutic effect of aceclofenac on rheumatoid arthritis and osteoarthritis.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s000110050571
