Niacin ameliorates ulcerative colitis via prostaglandin D2-mediated D prostanoid receptor 1 activation.
Niacin, as an antidyslipidemic drug, elicits a strong flushing response by release of prostaglandin (PG) D2However, whether niacin is beneficial for inflammatory bowel disease (IBD) remains unclear. Here, we observed niacin administration-enhanced PGD2production 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.
Department of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Juanjuan
J
Li
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Deping
D
Kong
Department of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Qi
Q
Wang
Department of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Wei
W
Wu
Department of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yanping
Y
Tang
Department of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Tingting
T
Bai
Department of Breast Surgery, Breast Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Liang
L
Guo
Department of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.|Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Lumin
L
Wei
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Qianqian
Q
Zhang
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Yu
Y
Yu
Department of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yuting
Y
Qian
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Shengkai
S
Zuo
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Guizhu
G
Liu
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Qian
Q
Liu
Department of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Sheng
S
Wu
Department of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yi
Y
Zang
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Qian
Q
Zhu
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Daile
D
Jia
Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Yuanyang
Y
Wang
Department of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Weiyan
W
Yao
The Key Laboratory of Cardiovascular Disease and Molecular Intervention, Atherosclerosis Research Centre, Nanjing Medical University, Nanjing Jiangsu, China.
Yong
Y
Ji
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Huiyong
H
Yin
Human Gene Sciences Center, Tokyo Medical and Dental University, Bunkyo-ku Tokyo, Japan.
Masataka
M
Nakamura
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba City Ibaraki, Japan.
Michael
M
Lazarus
Department of Veterans Affairs, Tennessee Valley Health Authority, Nashville, TN, USA.|Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Richard M
RM
Breyer
Department of Gastroenterology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China lifuwang@sjtu.edu.cn yuying@sibs.ac.cn yuying@tmu.edu.cn.
Lifu
0000-0001-5172-9932
L
Wang
Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China lifuwang@sjtu.edu.cn yuying@sibs.ac.cn yuying@tmu.edu.cn.|Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Ying
0000-0002-6476-1752
Y
Yu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009525:Niacin / Q000627:therapeutic use*; D015230:Prostaglandin D2 / Q000032:analysis / Q000276:immunology*; D011982:Receptors, Prostaglandin / Q000032:analysis / Q000276:immunology*; D014803:Vitamin B Complex / Q000627:therapeutic use*
D011982:Receptors, Prostaglandin; C527097:prostanoid D receptor 1, mouse; D014803:Vitamin B Complex; D009525:Niacin; D015230:Prostaglandin D2
DP1 receptor; niacin; prostaglandin; retention enema; ulcerative colitis