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Effects of anti-rheumatic treatments on expression of microsomal prostaglandin E synthase-1 in rheumatoid arthritis synovium

Background

mPGES-1 catalyzes the formation of PGE2 from COX-derived PGH2. mPGES-1 is induced by proinflammatory cytokines and linked to conditions with high PGE2 biosynthesis. Recent studies in animals suggest that mPGES-1 upregulation is involved in the pathogenesis of inflammatory arthritis, and thus has important clinical relevance for a better understanding and treatment of rheumatoid arthritis (RA).

Objective

Our aim was to study the effects of different antirheumatic therapies on expression of mPGES-1 in RA synovial tissue.

Methods

Synovial biopsies were taken by arthroscopy in patients with RA before and after TNF-blocking therapy with either etanercept (eight patients) or infliximab (10 patients), and in patients with chronic inflammatory arthritis before and after intra-articular injection of steroids (16 patients). Immunohistological analysis was performed using antibody against mPGES-1 and COX-2. Double immunofluorescence (DIF) was performed with antibodies to CD3, CD20, CD68, CD163 and prolyne-4-hydroxylase.

Results

mPGES-1 staining was detected in synovial lining cells, in sub-lining scattered cells in all patients, and in endothelial cells in few patients. DIF showed that mPGES-1 is produced in synovial macrophages and fibroblasts, whereas in lymphocytes mPGES-1 expression was not observed. TNF-blocking therapy has heterogeneous effects on the expression of mPGES-1, as well as COX-2 in synovial tissues. Intra-articular steroid treatment significantly reduced both mPGES-1 and COX-2 expression in synovial tissues (P < 0.05); however, the downregulation of mPGES-1 appears to be more prominent than that of COX-2.

Conclusion

The results demonstrate that corticosteroids but not TNF blockade downregulate mPGES-1. These data might be of importance for interpretation of effects of various therapies and provide support to the use of combination of TNF-blockade, corticosteroids, and nonsteroidal anti-inflammatory drugs.

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Korotkova, M., Westman, M., af Klint, E. et al. Effects of anti-rheumatic treatments on expression of microsomal prostaglandin E synthase-1 in rheumatoid arthritis synovium. Arthritis Res Ther 6 (Suppl 1), 98 (2004). https://doi.org/10.1186/ar1140

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  • DOI: https://doi.org/10.1186/ar1140

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