Role of prostaglandins in the loss of lymphatic contractile function in the experimental guinea pig model of TNBS‐induced ileitis

Abstract

The lymphatic vessel pumping is critical in maintaining tissue fluid homeostasis, particularly during edematous stress, such as inflammation. Loss of this function (i.e. dilated hyporesponsive lymphatic vessels) previously observed during experimental intestinal inflammation could be mediated by prostaglandins, which are heavily involved in the intestinal inflammatory response and potently alter lymphatic contractility. We thus evaluated the ability of lymphatics to synthesize and respond to prostaglandins in physiological and inflammatory conditions.Using real time PCR, we analyzed mesenteric lymphatics, arteries, veins, mesothelium and ileum obtained from control animals, TNBS‐treated guinea pigs and their sham counterpart for the following mRNA transcripts: COX‐1, COX‐2, prostacyclin synthase, prostaglandin E (PGE) synthase 1 and 2, prostacyclin receptor, and PGE2 receptors EP1, EP2, EP3 and EP4. We also measured PGE2 content in lymphatics by ELISA.When compared to sham and control animals, we observed an upregulation of COX‐2 mRNA and a downregulation of PGE synthase 2 and EP4 receptor mRNAs in lymphatics and ileum of TNBS‐treated animals. Preliminary data also showed an increase in PGE2 content in lymphatics from TNBS‐treated animals.Our results further suggest alteration of PGE2 function in lymphatics of TNBS‐treated guinea pigsSupported by the Crohn's and Colitis Foundation of Canada