The endogenous bioactive lipid prostaglandin D2-glycerol ester reduces murine colitis via DP1 and PPARγ receptors.

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.