The endogenous bioactive lipid prostaglandin D2‐glycerol ester reduces murine colitis via DP1 and PPARγ receptors. Issue 9 (9th April 2018)

• Record Type: Journal Article
• Authors: Alhouayek, Mireille; Buisseret, Baptiste; Paquot, Adrien; Guillemot-Legris, Owein; Muccioli, Giulio G.
• Is Part Of: FASEB journal. Volume 32:Issue 9(2018)
• Page Start: 5000
• Page End: 5011
• Publication Date: 2018-04-09
• Subjects: Crohn's disease -- eicosanoids -- prostanoid -- 15d-PGJ2-G; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201701205R
• Languages: English
• ISSNs: 0892-6638

Abstract

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 PGD2 ‐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 PGD2 ‐G with those of PGD2 and PGD2 ‐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 PGD2 ‐G is an agonist of the PGD2 receptor 1 (DP1) and that some of the effects of PGD2 ‐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 D2 ‐glycerol ester reduces murine colitis via DP1 and PPARγ receptors. FASEB J. 32, 5000–5011 (2018). www.fasebj.org