Inflammation Research

, Volume 60, Issue 12, pp 1083–1092

The cardinal role of the phospholipase A2/cyclooxygenase-2/prostaglandin E synthase/prostaglandin E2 (PCPP) axis in inflammostasis

Review

DOI: 10.1007/s00011-011-0385-7

Cite this article as:
Mancini, A.D. & Di Battista, J.A. Inflamm. Res. (2011) 60: 1083. doi:10.1007/s00011-011-0385-7

Abstract

The process of inflammation is regulated in part by bioactive lipids of which prostaglandins/eicosanoids form an important class. We provide evidence that the phospholipase A2/cyclooxygenase-2/prostaglandin E synthase/prostaglandin E2 (PCPP) axis is positioned at the core of a natural regulatory circuit controlling the initiation, magnitude, duration, and resolution of the inflammatory response. During the inflammatory phase, proinflammatory cytokine, chemokine and matrix destructive metalloprotease expression levels are moderated by the PCPP axis through the modulation of signaling pathways that control proinflammatory gene expression at transcriptional, post-transcriptional, and translational levels. The PCPP axis also contributes to the activation of lipid mediator class switching; this highly coordinated process results in the biosynthesis of lipoxins and resolvins that promote inflammatory resolution through a variety of cellular and molecular mechanisms. The PCPP axis activity is autoregulated by way of a positive feedback circuit involving PGE2-mediated, p38 MAPK-dependent stabilization of COX-2 mRNA and COX-2 catalytic potentiation via its limited proteolytic cleavage (e.g., Ca2+-activated calpains). In conclusion, through its fine temporal modulation of multiple signaling cassettes via EP1-EP4 GPCRs, PGE2 influences the onset, course, magnitude, and duration of the inflammatory response and functions as a key feedback regulator of the cellular and molecular processes controlling inflammation.

Keywords

COX-1/2 Prostaglandins Inflammatory mediators Models of joint inflammation RA 

Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Department of Anatomy and Cell BiologyMcGill UniversityMontrealCanada
  2. 2.Department of MedicineMcGill UniversityMontrealCanada
  3. 3.CRCHUM, Technopôle AngusMontrealCanada

Personalised recommendations