Protective effects of tranilast on oxazolone-induced rat colitis through a mast cell-dependent pathway

被引:15
作者
Chu, Hong-Qian [1 ,2 ]
Li, Jun [3 ]
Huang, Hong-Peng [1 ,2 ]
Hao, Wei-Dong [1 ,2 ]
Duan, Li-Ping [3 ]
Wei, Xue-Tao [1 ,2 ]
机构
[1] Peking Univ, Sch Publ Hlth, Dept Toxicol, Beijing 100871, Peoples R China
[2] Beijing Key Lab Toxicol Res & Risk Assessment Foo, Beijing, Peoples R China
[3] Peking Univ, Hosp 3, Dept Gastroenterol, Beijing 100871, Peoples R China
关键词
IL-33; Mast cell; Tranilast; Ulcerative colitis; INFLAMMATORY-BOWEL-DISEASE; TNBS-INDUCED COLITIS; ULCERATIVE-COLITIS; INDUCED ARTHRITIS; EPITHELIAL-CELLS; IL-13; PRODUCTION; MURINE MODEL; CANCER; IL-33; MICE;
D O I
10.1016/j.dld.2015.09.002
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Mast cells in the gut play an important role in the innate and adaptive immune responses that are relevant to human inflammatory bowel disease. However, the contribution of mast cells to the development of inflammatory bowel disease is not well understood. This study aimed to determine the role of mast cells in oxazolone-induced colitis and to explore whether the mast cell membrane stabiliser tranilast could ameliorate colonic inflammation. Methods: Wild-type rats and mast cell-deficient rats were sensitised and challenged with oxazolone, then treated with tranilast after challenge. Controls were treated with saline. Results: Mast cell-deficient rats presented a weak response to oxazolone, while wild-type rats showed severe ulcerative colitis after stimulation with oxazolone. The mast cell-deficient rats model had a significantly lower disease activity index score than wild-type rats model (1.8 +/- 1.64 vs 8.3 +/- 0.58 respectively; P < 0.01). Tranilast could reduce the secretion of cytokines, immunoglobulins and myeloperoxidase activity in tranilast treatment groups compared with the model group. The number of mast cells in the wild-type model was higher than in the other groups. There was no significant change in mast cell-deficient rats. Conclusion: Mast cells play an important role in oxazolone-induced colitis. The mast cell membrane stabiliser tranilast can ameliorate oxazolone-induced colitis via a mast cell-dependent pathway. (C) 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:162 / 171
页数:10
相关论文
共 42 条
[1]   Functional gastrointestinal disorders and mast cells: implications for therapy [J].
Barbara, G ;
Stanghellini, V ;
De Giorgio, R ;
Corinaldesi, R .
NEUROGASTROENTEROLOGY AND MOTILITY, 2006, 18 (01) :6-17
[2]   Oxazolone colitis: A murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4 [J].
Boirivant, M ;
Fuss, IJ ;
Chu, A ;
Strober, W .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 188 (10) :1929-1939
[3]   Increased responsiveness of rat colonic splanchnic afferents to 5-HT after inflammation and recovery [J].
Coldwell, Jonathan R. ;
Phillis, Benjamin D. ;
Sutherland, Kate ;
Howarth, Gordon S. ;
Blackshaw, L. Ashley .
JOURNAL OF PHYSIOLOGY-LONDON, 2007, 579 (01) :203-213
[4]   Tranilast enhances the anti-tumor effects of tamoxifen on human breast cancer cells in vitro [J].
Darakhshan, Sara ;
Ghanbari, Ali .
JOURNAL OF BIOMEDICAL SCIENCE, 2013, 20
[5]   Review article: gastrointestinal sensory and motor disturbances in inflammatory bowel disease - clinical relevance and pathophysiological mechanisms [J].
De Schepper, H. U. ;
De Man, J. G. ;
Moreels, T. G. ;
Pelckmans, P. A. ;
De Winter, B. Y. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2008, 27 (08) :621-637
[6]   Oxazolone-induced colitis in rats:: Effects of budesonide, cyclosporin A, and 5-aminosalicylic acid acid [J].
Ekström, GM .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 1998, 33 (02) :174-179
[7]  
Ekström GM, 2000, SCAND J GASTROENTERO, V35, P190
[8]   KETOTIFEN EFFECTIVELY PREVENTS MUCOSAL DAMAGE IN EXPERIMENTAL COLITIS [J].
ELIAKIM, R ;
KARMELI, F ;
OKON, E ;
RACHMILEWITZ, D .
GUT, 1992, 33 (11) :1498-1503
[9]   Opposite effects of substance P and calcitonin gene-related peptide in oxazolone colitis [J].
Engel, Matthias A. ;
Khalil, Mohammad ;
Siklosi, Norbert ;
Mueller-Tribbensee, Sonja M. ;
Neuhuber, Winfried L. ;
Neurath, Markus F. ;
Becker, Christoph ;
Reeh, Peter W. .
DIGESTIVE AND LIVER DISEASE, 2012, 44 (01) :24-29
[10]   Interleukin-6, a Major Cytokine in the Central Nervous System [J].
Erta, Maria ;
Quintana, Albert ;
Hidalgo, Juan .
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES, 2012, 8 (09) :1254-1266