Niacin ameliorates ulcerative colitis via prostaglandin D(2)-mediated D prostanoid receptor 1 activation.
Niacin ameliorates ulcerative colitis via prostaglandin D(2)-mediated D prostanoid receptor 1 activation.
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DOI：
10.15252/emmm.201606987
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发表时间：
2017-05
影响因子：
11.1
通讯作者：
Yu Y
中科院分区：
文献类型：
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作者：
Li J;Kong D;Wang Q;Wu W;Tang Y;Bai T;Guo L;Wei L;Zhang Q;Yu Y;Qian Y;Zuo S;Liu G;Liu Q;Wu S;Zang Y;Zhu Q;Jia D;Wang Y;Yao W;Ji Y;Yin H;Nakamura M;Lazarus M;Breyer RM;Wang L;Yu Y
烟酸作为一种降血脂药物，通过释放前列腺素D2而引起强烈的潮红反应。然而，烟酸对炎症性肠病(IBD)是否有益仍不清楚。在此，我们观察了烟酸对葡聚糖硫酸钠(DSS)攻击小鼠结肠组织中PGD2产生的促进作用，并以D前列腺素受体1(DP1)依赖的方式保护小鼠免受DSS或2，4，6-三硝基苯磺酸(TNBS)诱导的结肠炎。特异性阻断血管内皮细胞、结肠上皮细胞和髓样细胞中的DP1受体分别通过增加血管通透性、促进上皮细胞凋亡和刺激巨噬细胞分泌促炎细胞因子来增强DSS/TNBS诱导的小鼠结肠炎。烟酸治疗可改善血管通透性，减少上皮细胞凋亡，促进上皮细胞更新，抑制巨噬细胞促炎基因表达。此外，含有烟酸的保留灌肠治疗有效地促进了中度活动期疾病患者的UC临床缓解和粘膜愈合。因此，烟酸通过激活PGD2/DP1轴对DSS/TNBS诱导的小鼠结肠炎具有多方面的有益作用。烟酸治疗IBD的潜在疗效值得进一步研究。
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.