title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Karolinska Hospital, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Westman
authors.forename: M
authors.initials: M
authors.lastname: Korotkova
authors.forename: E
authors.initials: E
authors.lastname: af Klint
authors.forename: A
authors.initials: A
authors.lastname: Stark
authors.forename: L P
authors.initials: LP
authors.lastname: Audoly
authors.forename: L
authors.initials: L
authors.lastname: Klareskog
authors.forename: A-K
authors.initials: AK
authors.lastname: Ulfgren
authors.forename: P-J
authors.initials: PJ
authors.lastname: Jakobsson
mesh_terms: D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D015232:Dinoprostone / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000276:immunology / Q000378:metabolism*; D008861:Microsomes / Q000201:enzymology; D000071876:Prostaglandin-E Synthases; D013583:Synovial Membrane / Q000201:enzymology* / Q000473:pathology
chemical_list: D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone