Expression of microsomal prostaglandin E synthase 1 in RA synovium

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Arthritis Rheum. 2004 Jun;50(6):1774-80.

Expression of microsomal prostaglandin E synthase 1 in rheumatoid

arthritis synovium.

Westman M, Korotkova M, af Klint E, Stark A, Audoly LP, Klareskog L,

Ulfgren AK, Jakobsson PJ.

Karolinska Hospital, Stockholm, Sweden.

OBJECTIVE: Microsomal prostaglandin E synthase 1 (mPGES-1) catalyzes the

formation of PGE(2) from cyclooxygenase-derived PGH(2). Microsomal

PGES-1 is induced by proinflammatory cytokines and is strongly linked to

conditions that result in high PGE(2) biosynthesis. PGE(2) 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 PGE(2) synthesis in patients with RA, without the

systemic side effects associated with cyclooxygenase inhibitors.

PMID: 15188353

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