Niacin ameliorates ulcerative colitis via prostaglandin D2-mediated D prostanoid receptor 1 activation.

Abstract

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.

• Authors: Juanjuan Li, Deping Kong, Qi Wang, Wei Wu, Yanping Tang, Tingting Bai, Liang Guo, Lumin Wei, Qianqian Zhang, Yu Yu, Yuting Qian, Shengkai Zuo, Guizhu Liu, Qian Liu, Sheng Wu, Yi Zang, Qian Zhu, Daile Jia, Yuanyang Wang, Weiyan Yao, Yong Ji, Huiyong Yin, Masataka Nakamura, Michael Lazarus, Richard M Breyer, Lifu Wang, Ying Yu
• Journal: EMBO molecular medicine (EMBO Mol Med) Vol. 9 Issue 5 Pg. 571-588 (05 2017) ISSN: 1757-4684 [Electronic] England
• PMID: 28341703 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Chemical References

• Receptors, Prostaglandin
• prostanoid D receptor 1, mouse
• Vitamin B Complex
• Niacin
• Prostaglandin D2

Topics

• Animals
• Apoptosis (drug effects)
• Capillary Permeability (drug effects)
• Colitis, Ulcerative (drug therapy, immunology, pathology)
• Humans
• Intestinal Mucosa (drug effects, immunology, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Niacin (therapeutic use)
• Prostaglandin D2 (analysis, immunology)
• Receptors, Prostaglandin (analysis, immunology)
• Vitamin B Complex (therapeutic use)