Premium
Rectal administration of tranilast ameliorated acute colitis in mice through increased expression of heme oxygenase‐1
Author(s) -
Sun Xiaomei,
Suzuki Kenji,
Nagata Masaki,
Kawauchi Yusuke,
Yano Masahiko,
Ohkoshi Shogo,
Matsuda Yasunobu,
Kawachi Hiroshi,
Watanabe Kenichi,
Asakura Hitoshi,
Aoyagi Yutaka
Publication year - 2010
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/j.1440-1827.2009.02490.x
Subject(s) - tranilast , medicine , colitis , degranulation , inflammatory bowel disease , heme oxygenase , tumor necrosis factor alpha , mast cell , pharmacology , immunology , heme , chemistry , disease , receptor , biochemistry , enzyme
Mast cells play a key role in the pathophysiology of inflammatory bowel disease (IBD). Tranilast, a mast cell stabilizer, has been empirically used for IBD in Japan, but its precise role in the treatment of IBD is largely unknown. To investigate the role of tranilast for the treatment of IBD, tranilast was administered intrarectally to mice with dextran sulfate sodium (DSS)‐induced colitis. Tranilast ameliorated DSS colitis clinically and pathologically, as demonstrated by decreased number and degranulation of mast cells in the colon. mRNA expression was increased for tumor necrosis factor‐α, interferon‐γ and interleukin (IL)‐6, and decreased for IL‐10 in the colon of DSS colitis mice. In contrast, tranilast markedly decreased expression of mRNAs for the pro‐inflammatory cytokines, and increased that of the anti‐inflammatory cytokines. Moreover, tranilast increased heme oxygenase (HO)‐1 expression on colonic epithelial cells as well as on colon‐infiltrating cells of DSS colitis. In conclusion, tranilast ameliorated DSS colitis by regulating mast cell degranulation, decreasing inflammatory cytokines and increasing anti‐inflammatory cytokines. Tranilast might exert these effects partly through enhanced HO‐1 expression in the colon, suggesting a potential adjunctive therapy for IBD.