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 dextr...

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Main 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
Format: Article
Language:English
Published: Springer Nature 2017-03-01
Series:EMBO Molecular Medicine
Subjects:
Online Access:https://doi.org/10.15252/emmm.201606987
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author 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
author_facet 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
author_sort Juanjuan Li
collection DOAJ
description 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.
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spelling doaj-art-b98e9055c3c040d48995bb25f39bd9ab2025-08-20T04:03:07ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842017-03-019557158810.15252/emmm.201606987Niacin ameliorates ulcerative colitis via prostaglandin D2‐mediated D prostanoid receptor 1 activationJuanjuan Li0Deping Kong1Qi Wang2Wei Wu3Yanping Tang4Tingting Bai5Liang Guo6Lumin Wei7Qianqian Zhang8Yu Yu9Yuting Qian10Shengkai Zuo11Guizhu Liu12Qian Liu13Sheng Wu14Yi Zang15Qian Zhu16Daile Jia17Yuanyang Wang18Weiyan Yao19Yong Ji20Huiyong Yin21Masataka Nakamura22Michael Lazarus23Richard M Breyer24Lifu Wang25Ying Yu26Department of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineKey Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesDepartment of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Breast Surgery, Breast Cancer Institute, Fudan University Shanghai Cancer CenterDepartment of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineKey Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesKey Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesDepartment of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineKey Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesKey Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesKey Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesDepartment of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineDepartment of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineKey Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesKey Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesDepartment of Pharmacology, School of Basic Medical Sciences, Tianjin Medical UniversityDepartment of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineThe Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, NanjingKey Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesHuman Gene Sciences Center, Tokyo Medical and Dental University, Bunkyo‐kuInternational Institute for Integrative Sleep Medicine (WPI‐IIIS), University of Tsukuba, Tsukuba CityDepartment of Veterans Affairs, Tennessee Valley Health AuthorityDepartment of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of MedicineKey Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesAbstract 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.https://doi.org/10.15252/emmm.201606987DP1 receptorniacinprostaglandinretention enemaulcerative colitis
spellingShingle 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
Niacin ameliorates ulcerative colitis via prostaglandin D2‐mediated D prostanoid receptor 1 activation
EMBO Molecular Medicine
DP1 receptor
niacin
prostaglandin
retention enema
ulcerative colitis
title Niacin ameliorates ulcerative colitis via prostaglandin D2‐mediated D prostanoid receptor 1 activation
title_full Niacin ameliorates ulcerative colitis via prostaglandin D2‐mediated D prostanoid receptor 1 activation
title_fullStr Niacin ameliorates ulcerative colitis via prostaglandin D2‐mediated D prostanoid receptor 1 activation
title_full_unstemmed Niacin ameliorates ulcerative colitis via prostaglandin D2‐mediated D prostanoid receptor 1 activation
title_short Niacin ameliorates ulcerative colitis via prostaglandin D2‐mediated D prostanoid receptor 1 activation
title_sort niacin ameliorates ulcerative colitis via prostaglandin d2 mediated d prostanoid receptor 1 activation
topic DP1 receptor
niacin
prostaglandin
retention enema
ulcerative colitis
url https://doi.org/10.15252/emmm.201606987
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