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

Andrey Frolov, Lihua Yang, Hua Dong, Bruce D. Hammock, Leslie J. Crofford

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)351-358
Number of pages8
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Volume89
Issue number5
DOIs
StatePublished - Oct 2013

Fingerprint

Prostaglandins E
Dinoprostone
Arthritis
Anti-Inflammatory Agents
Experimental Arthritis
Neutrophils
Collagen
Inflammation
Inflammation Mediators
Collagen Type II
Antibodies
Macrophages
Liquid chromatography
Adaptive Immunity
Tandem Mass Spectrometry
Prostaglandin-E Synthases
Liquid Chromatography
Autoantibodies
Prostaglandins
Mass spectrometry

Keywords

  • Arthritis
  • Inflammation
  • mPGES-1
  • Prostaglandin

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry

Cite this

Anti-inflammatory properties of prostaglandin E2 : Deletion of microsomal prostaglandin E synthase-1 exacerbates non-immune inflammatory arthritis in mice. / Frolov, Andrey; Yang, Lihua; Dong, Hua; Hammock, Bruce D.; Crofford, Leslie J.

In: Prostaglandins Leukotrienes and Essential Fatty Acids, Vol. 89, No. 5, 10.2013, p. 351-358.

Research output: Contribution to journalArticle

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