Niacin ameliorates ulcerative colitis via prostaglandin D ₂ ‐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.

The endogenous bioactive lipid prostaglandin D 2 ‐glycerol ester reduces murine colitis via DP1 and PPARγ receptors

“…Indeed, BW245C, a DP1 agonist, was shown to decrease colitis as well as the incidence of colitis-associated cancer in the DSS-azoxymethane model of colitis-associated cancer (7), whereas a DP1 antagonist worsened DSS-induced colitis (8). Moreover, 1 study showed that niacin administration to mice with DSS-and TNBS-induced colitis leads to an increase of PGD 2 production and subsequently to a decrease in colitis severity in a DP1-dependent manner (41). These studies point to a beneficial effect of DP1 in colitis that PGD 2 -G could be part of.…”

Eicosanoids in tissue repair

“…This review aims to provide an overview of the roles of eicosanoids in physiological as well as pathogenic situations of tissue repair. As eicosanoids produced via the cyclooxygenase (COX) pathway (prostanoids) play particularly important roles in tissue repair, these mediators will be discussed in detail and with a focus on recent insights into their involvement in the repair of epithelial barriers …”

“…Newly deposited ECM then undergoes structural "remodeling" and the inflammatory response is terminated [e.g. by the action of lipoxin A 4 (LXA 4 )], thus resulting in "resolution" and the formation of new functional tissue.…”

“…As eicosanoids produced via the cyclooxygenase (COX) pathway (prostanoids) play particularly important roles in tissue repair, these mediators will be discussed in detail and with a focus on recent insights into their involvement in the repair of epithelial barriers. 4,5 Total and conditional knock-outs of eicosanoid pathway components in mice have provided detailed mechanistic insights into the contribution of individual metabolites and receptors to tissue repair. These studies showed that COX metabolites (e.g.…”

“…prostaglandin E 2 ) can accelerate repair, whereas LTs produced via the 5lipoxygenase (5-LOX) pathway can impair tissue repair and instead cause aberrant inflammation and tissue ( Table 1). [4][5][6][7] In contrast to the detrimental role of proinflammatory 5-LOX metabolites, anti-inflammatory metabolites of 12/15-LOX (e.g. LXA 4 ) can reduce inflammation and promote tissue repair.…”