Rectal administration of tranilast ameliorated acute colitis in mice through increased expression of heme oxygenase-1.
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-alpha, interferon-gamma 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.
Sun
Xiaomei
X
Department of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Suzuki
Kenji
K
Nagata
Masaki
M
Kawauchi
Yusuke
Y
Yano
Masahiko
M
Ohkoshi
Shogo
S
Matsuda
Yasunobu
Y
Kawachi
Hiroshi
H
Watanabe
Kenichi
K
Asakura
Hitoshi
H
Aoyagi
Yutaka
Y
D000285:Administration, Rectal; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D015550:Cell Degranulation / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000187:drug effects; D016264:Dextran Sulfate / Q000633:toxicity; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000187:drug effects*; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D062367:ortho-Aminobenzoates / Q000008:administration & dosage*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D012333:RNA, Messenger; D062367:ortho-Aminobenzoates; D016264:Dextran Sulfate; D051547:Heme Oxygenase-1; C012293:tranilast