Niacin ameliorates ulcerative colitis via prostaglandin D2‐mediated D prostanoid receptor 1 activation
نویسندگان
چکیده
Niacin, as an antidyslipidemic drug, elicits a strong flushing response by release of prostaglandin (PG) D2 However, whether niacin is beneficial for inflammatory bowel disease (IBD) remains unclear. Here, we observed niacin administration-enhanced PGD2 production in colon tissues in dextran sulfate sodium (DSS)-challenged mice, and protected mice against DSS or 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in D prostanoid receptor 1 (DP1)-dependent manner. Specific ablation of DP1 receptor in vascular endothelial cells, colonic epithelium, and myeloid cells augmented DSS/TNBS-induced colitis in mice through increasing vascular permeability, promoting apoptosis of epithelial cells, and stimulating pro-inflammatory cytokine secretion of macrophages, respectively. Niacin treatment improved vascular permeability, reduced apoptotic epithelial cells, promoted epithelial cell update, and suppressed pro-inflammatory gene expression of macrophages. Moreover, treatment with niacin-containing retention enema effectively promoted UC clinical remission and mucosal healing in patients with moderately active disease. Therefore, niacin displayed multiple beneficial effects on DSS/TNBS-induced colitis in mice by activation of PGD2/DP1 axis. The potential efficacy of niacin in management of IBD warrants further investigation.
منابع مشابه
Niacin Promotes Cardiac Healing after Myocardial Infarction through Activation of the Myeloid Prostaglandin D2 Receptor Subtype 1.
Niacin is a well established drug used to lower cholesterol and prevent cardiovascular disease events. However, niacin also causes cutaneous flushing side effects due to release of the proresolution mediator prostaglandin D2 (PGD2). Recent randomized clinical trials have demonstrated that addition of niacin with laropiprant [a PGD2 receptor subtype 1 (DP1) blocker] to statin-based therapies doe...
متن کاملProstaglandin D2 receptor D-type prostanoid receptor 2 mediates eosinophil trafficking into the esophagus.
Eosinophilic esophagitis is characterized by eosinophil-predominant inflammation in the esophagus. How eosinophils migrate and infiltrate into the esophagus, however, is less clear. Our previous study demonstrated that mast cell activation led to eosinophil infiltration in the esophagus. Prostaglandin D2 (PGD2) is an important mediator released from activated mast cells. The present study aims ...
متن کاملProstaglandins and Their Receptors in Eosinophil Function and As Therapeutic Targets
Of the known prostanoid receptors, human eosinophils express the prostaglandin D2 (PGD2) receptors DP1 [also D-type prostanoid (DP)] and DP2 (also chemoattractant receptor homologous molecule, expressed on Th2 cells), the prostaglandin E2 receptors EP2 and EP4, and the prostacyclin (PGI2) receptor IP. Prostanoids can bind to either one or multiple receptors, characteristically have a short half...
متن کاملProstanoid synthesis by cultured intestinal epithelial and mononuclear cells in inflammatory bowel disease.
Intestinal epithelial and mononuclear cells were isolated from normal colonic mucosa and from intestinal mucosa of inflammatory bowel disease patients. Prostanoid synthesis by primary cultures of intestinal mononuclear cells were four to six fold higher than its synthesis by primary cultures of epithelial cells. Prostaglandin E2, prostacyclin and thromboxane A2 synthesis by cultured mononuclear...
متن کاملThe D-type prostanoid (DP) receptor enhances the signaling of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2)
Background Prostaglandin (PG) D2 is substantially involved in allergic responses and signals via the seven-transmembranespanning/G protein-coupled receptors, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) and D-type prostanoid (DP) receptor. While the proinflammatory function of CRTH2 is well recognized and CRTH2 is hence considered as an important emerging pharmaco...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 9 شماره
صفحات -
تاریخ انتشار 2017