Expression of microsomal prostaglandin E synthase 1 in rheumatoid arthritis synovium

Abstract

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.

Inhibition of microsomal prostaglandin E2 synthase‐1 as a molecular basis for the anti‐inflammatory actions of boswellic acids from frankincense

“…zileuton) and studies on 5-LOX-or 5-LOXactivating protein-deficient mice, exclude a prominent role of LTs in OA or RA (Werz and Steinhilber, 2006). However, PGE2 is a key mediator accounting for typical disease symptoms in OA and RA (Smith, 1989); and in patients suffering from RA or OA, a pivotal role for mPGES1 has been demonstrated (Westman et al, 2004;Li et al, 2005). Moreover, data from animal arthritis models support the relevance of mPGES1 to inflammatory joint diseases (Claveau et al, 2003;Trebino et al, 2003;Guay et al, 2004).…”

Evidence for interaction between 5-hydroxytryptamine (serotonin) receptor 2A and MHC type II molecules in the development of rheumatoid arthritis

“…Double immunofluorescence staining was performed using mouse monoclonal anti-HLA-DR (BD Biosciences) and rabbit polyclonal anti-5-HT2A antibodies (Sigma Chemicals) as published previously. 29 …”

Inhibition of Matrix Metalloproteinase-3 and -13 Synthesis Induced by IL-1β in Chondrocytes from Mice Lacking Microsomal Prostaglandin E Synthase-1

“…Previous studies demonstrated that IL-1b markedly increased mPGES-1 mRNA and protein expression, in parallel with an increase in PGE 2 levels in chondrocytes (9,10). Interestingly, accumulating evidences involve mPGES-1 in cartilage degradation (9)(10)(11)(12)(13)(14).…”