Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
FASEB J. 2018 Sep;32(9):5000-5011. doi: 10.1096/fj.201701205R. Epub 2018 Apr 9.
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-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-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-G with those of PGD and PGD-EA. Finally, we used receptor antagonists to gain mechanistic insight into the receptors responsible for the observed effects. PGD-G reduced DSS-induced colitis, but PGD and PGD-EA did not have the same effect. Furthermore, we showed that PGD-G is an agonist of the PGD receptor 1 (DP1) and that some of the effects of PGD-G were blocked by antagonism of peroxisome proliferator-activated receptor γ and DP1. Therefore, PGD-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-glycerol ester reduces murine colitis via DP1 and PPARγ receptors.
环氧化酶-2（COX-2）长期以来一直被认为与炎症性肠病（IBD）的发病机制有关。COX-2 主要通过花生四烯酸产生前列腺素（PGs）。然而，它还将内源性大麻素 2-花生四烯酸甘油（2-AG）和大麻酰胺代谢为研究较少的生物活性脂质 PG-甘油酯（PG-Gs）和 PG-乙醇酰胺（PG-EAs 或前列腺素）。我们之前表明，COX-2 氧化 2-AG 的产物 PGD-G 具有抗炎作用。因此，我们使用葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型来探索 PGD-G 在 IBD 小鼠模型中的作用。通过宏观和组织学评分、髓过氧化物酶活性以及实时定量 PCR 和 ELISA 评估炎症介质的表达来评估结肠炎症。我们还比较了 PGD-G 与 PGD 和 PGD-EA 的作用。最后，我们使用受体拮抗剂深入了解负责观察到的作用的受体。PGD-G 可减轻 DSS 诱导的结肠炎，但 PGD 和 PGD-EA 没有相同的作用。此外，我们表明 PGD-G 是 PGD 受体 1（DP1）的激动剂，并且 PGD-G 的一些作用被过氧化物酶体增殖物激活受体 γ 和 DP1 的拮抗剂阻断。因此，PGD-G 可能是 COX-2/前列腺素 D 合酶轴的产物之一，可在结肠炎中发挥有益作用。-Alhouayek，M.，Buisseret，B.，Paquot，A.，Guillemot-Legris，O.，Muccioli，G. G. 内源性生物活性脂质前列腺素 D-甘油酯通过 DP1 和 PPARγ 受体减轻小鼠结肠炎。
