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Ann Rheum Dis. 2004 Nov;63(11):1453-9.

Effects of RWJ 67657, a p38 mitogen activated protein kinase (MAPK) inhibitor, on the production of inflammatory mediators by rheumatoid synovial fibroblasts.

Author information

  • 1Department of Rheumatology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, Netherlands. j.westra@med.rug.nl

Abstract

OBJECTIVE:

To investigate the effect of the p38 mitogen activated protein kinase (MAPK) inhibitor RWJ 67657 on inflammatory mediator production by rheumatoid synovial fibroblasts (RSF).

METHODS:

RSF were pretreated with RWJ 67657 and stimulated with TNF alpha and/or IL-1 beta. Protein levels and mRNA expression of MMP-1, MMP-3, TIMP-1, IL-6, and IL-8 were determined, as was mRNA expression of COX-2 and ADAMTS-4.

RESULTS:

MMP-3 production was significantly inhibited at 1 microM RWJ 67657 and MMP-1 production at 10 microM, while TIMP-1 production was not inhibited. Inhibition of IL-6 and IL-8 protein production was seen at 0.1 microM RWJ 67657. Expression profiles of mRNA were in accordance with protein production. Inhibition of COX-2 mRNA expression occurred at 0.01 microM RWJ 67657.

CONCLUSIONS:

RWJ 67657 inhibits major proinflammatory mediator production in stimulated RSF at pharmacologically relevant concentrations. These findings could have important relevance for the treatment of rheumatoid arthritis.

PMID:
15479895
PMCID:
PMC1754789
DOI:
10.1136/ard.2003.013011
[PubMed - indexed for MEDLINE]
Free PMC Article
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