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

EMBO Mol Med. 2017 May;9(5):571-588. doi: 10.15252/emmm.201606987.

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.

Keywords: DP1 receptor; niacin; prostaglandin; retention enema; ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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