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The endogenous bioactive lipid prostaglandin D 2 ‐glycerol ester reduces murine colitis via DP1 and PPARγ receptors
Author(s) -
Alhouayek Mireille,
Buisseret Baptiste,
Paquot Adrien,
Guillemot-Legris Owein,
Muccioli Giulio G.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201701205r
Subject(s) - endocannabinoid system , chemistry , colitis , prostaglandin d2 , prostaglandin , receptor , cyclooxygenase , palmitoylethanolamide , pharmacology , anandamide , agonist , lipid signaling , cannabinoid receptor , eicosanoid , inflammation , arachidonic acid , prostaglandin e , biochemistry , endocrinology , medicine , biology , enzyme
ABSTRACT 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 PGD2‐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. PGD2‐G reduced DSS‐induced colitis, but PGD2 and PGD2‐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 γ and DP1. Therefore, PGD2‐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 PPARγ receptors. FASEB J. 32, 5000–5011 (2018). www.fasebj.org