Anti-inflammatory properties of prostaglandin E2: deletion of microsomal prostaglandin E synthase-1 exacerbates non-immune inflammatory arthritis in mice.

Frolov A, Yang L, Dong H, Hammock BD, Crofford LJ
Prostaglandins Leukot Essent Fatty Acids. 2013 89 (5): 351-8

PMID: 24055573 · PMCID: PMC3897272 · DOI:10.1016/j.plefa.2013.08.003

Prostanoids and PGE2 in particular have been long viewed as one of the major mediators of inflammation in arthritis. However, experimental data indicate that PGE2 can serve both pro- and anti-inflammatory functions. We have previously shown (Kojima et al., J. Immunol. 180 (2008) 8361-8368) that microsomal prostaglandin E synthase-1 (mPGES-1) deletion, which regulates PGE2 production, resulted in the suppression of collagen-induced arthritis (CIA) in mice. This suppression was attributable, at least in part, to the impaired generation of type II collagen autoantibodies. In order to examine the function of mPGES-1 and PGE2 in a non-autoimmune form of arthritis, we used the collagen antibody-induced arthritis (CAIA) model in mice deficient in mPGES-1, thereby bypassing the engagement of the adaptive immune response in arthritis development. Here we report that mPGES-1 deletion significantly increased CAIA disease severity. The latter was associated with a significant (~3.6) upregulation of neutrophil, but not macrophage, recruitment to the inflamed joints. The lipidomic analysis of the arthritic mouse paws by quantitative liquid chromatography/tandem mass-spectrometry (LC/MS/MS) revealed a dramatic (~59-fold) reduction of PGE2 at the peak of arthritis. Altogether, this study highlights mPGES-1 and its product PGE2 as important negative regulators of neutrophil-mediated inflammation and suggests that specific mPGES-1 inhibitors may have differential effects on different types of inflammation. Furthermore, neutrophil-mediated diseases could be exacerbated by inhibition of mPGES-1.

© 2013 Published by Elsevier Ltd.

MeSH Terms (20)

Animals Arthritis, Experimental Autoantibodies Chromatography, Liquid Collagen Type II Dinoprostone Female Gene Deletion Inflammation Intramolecular Oxidoreductases Joints Lipid Metabolism Macrophages Male Mice Neutrophil Infiltration Neutrophils Prostaglandin-E Synthases Severity of Illness Index Tandem Mass Spectrometry

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