Expression of microsomal prostaglandin E synthase 1 in rheumatoid arthritis synovium

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Abstract
Objective Microsomal prostaglandin E synthase 1 (mPGES‐1) catalyzes the formation of PGE2 from cyclooxygenase‐derived PGH2. Microsomal PGES‐1 is induced by proinflammatory cytokines and is strongly linked to conditions that result in high PGE2 biosynthesis. PGE2 contributes to the pathogenesis of rheumatoid arthritis (RA), acting as a mediator of inflammation and promoting bone destruction. Induction of mPGES‐1 in rheumatoid synoviocytes by proinflammatory cytokines has been demonstrated in vitro, indicating an important role in RA pathogenesis. Recent studies using mPGES‐1–deficient mice demonstrated the importance of this gene in chronic inflammation. The aim of this study was to investigate the expression and localization of mPGES‐1 in synovial biopsy specimens obtained from patients with RA. Methods Synovial tissue samples from 24 patients with RA were obtained, and immunohistologic analysis was performed using polyclonal antibodies against mPGES‐1. Double immunofluorescence staining was performed with antibodies to CD3, CD19, CD20, CD68, CD163, and prolyl 4‐hydroxylase. Results Intracellular mPGES‐1 staining was observed in synovial membranes from all of the RA patients studied. Specifically, strong expression of mPGES‐1 was detected in synovial lining cells. In sublining mononuclear and fibroblast‐like cells, the extent of mPGES‐1 staining was less than that in the synovial lining cells. In some patients, positive staining was observed in endothelial cells. With the double immunofluorescence technique, mPGES‐1 production was detected in synovial macrophages and fibroblasts, while mPGES‐1 expression was not observed in lymphocytes. Conclusion The demonstration of mPGES‐1 expression in synovial tissues from patients with RA suggests a role for mPGES‐1 in the RA disease process. Microsomal PGES‐1 might be a potential new target for treatment strategies to control PGE2 synthesis in patients with RA, without the systemic side effects associated with cyclooxygenase inhibitors.

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