Journal
FASEB JOURNAL
Volume 32, Issue 9, Pages 5000-5011Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201701205R
Keywords
Crohn's disease; eicosanoids; prostanoid; 15d-PGJ2-G
Categories
Funding
- European Crohn's and Colitis Organisation (ECCO) [J.0071.15]
- FRS-FNRS (Belgium)
- FRS-FNRS (Fonds National de la Recherche Scientifique), Belgium
- European Crohn's and Colitis Organisation (ECCO)
- FRS-FNRS (Belgium) [J.0071.15]
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Cyclooxygenase-2 (COX-2) has long been implicated in the pathogenesis of inflammatory bowel diseases (IBDs). COX-2 is mostly known for the production of prostaglandins (PGs) from arachidonic acid. However, it also metabolizes the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide into the less well-studied bioactive lipids PG-glycerol esters (PG-Gs) and PG-ethanolamides (PG-EAs or prostamides). We previously showed that PGD(2)-G, a product of 2-AG oxygenation by COX-2, has anti-inflammatory effects. Therefore, we used the dextran sulfate sodium (DSS)-induced model of colitis in mice to explore the role of PGD(2)-G in murine models of IBD. Colon inflammation was assessed using macroscopic and histologic scores, myeloperoxidase activity, and expression of inflammatory mediators by real-time quantitative PCR and ELISA. We also compared the effects of PGD(2)-G with those of PGD(2) and PGD(2)-EA. Finally, we used receptor antagonists to gain mechanistic insight into the receptors responsible for the observed effects. PGD(2)-G reduced DSS-induced colitis, but PGD(2) and PGD(2)-EA did not have the same effect. Furthermore, we showed that PGD(2)-G is an agonist of the PGD(2) receptor 1 (DP1) and that some of the effects of PGD(2)-G were blocked by antagonism of peroxisome proliferator-activated receptor and DP1. Therefore, PGD(2)-G could be one of the products from the COX-2/prostaglandin D synthase axis to exert beneficial effects in colitis.Alhouayek, M., Buisseret, B., Paquot, A., Guillemot-Legris, O., Muccioli, G. G. The endogenous bioactive lipid prostaglandin D-2-glycerol ester reduces murine colitis via DP1 and PPAR receptors.
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