caa a22 4500 44588536X CHVBK 20180317145557.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s00011-011-0385-7 doi (NATIONALLICENCE)springer-10.1007/s00011-011-0385-7 The cardinal role of the phospholipase A2/cyclooxygenase-2/prostaglandin E synthase/prostaglandin E2 (PCPP) axis in inflammostasis [Elektronische Daten] [A. Mancini, J. Di Battista] 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. Springer Basel AG, 2011 COX-1/2 nationallicence Prostaglandins nationallicence Inflammatory mediators nationallicence Models of joint inflammation nationallicence RA nationallicence Mancini A. Department of Anatomy and Cell Biology, McGill University, 3640 University St, H3A 2B2, Montreal, QC, Canada aut Di Battista J. Department of Medicine, McGill University, 687 Pine Ave, H3A 1A1, Montreal, QC, Canada aut Inflammation Research SP Birkhäuser Verlag Basel 60/12(2011-12-01), 1083-1092 1023-3830 60:12<1083 2011 60 11 https://doi.org/10.1007/s00011-011-0385-7 text/html Onlinezugriff via DOI 1 review-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00011-011-0385-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mancini A. Department of Anatomy and Cell Biology, McGill University, 3640 University St, H3A 2B2, Montreal, QC, Canada aut NATIONALLICENCE 700 1- Di Battista J. Department of Medicine, McGill University, 687 Pine Ave, H3A 1A1, Montreal, QC, Canada aut NATIONALLICENCE 773 0- Inflammation Research SP Birkhäuser Verlag Basel 60/12(2011-12-01), 1083-1092 1023-3830 60:12<1083 2011 60 11 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer