論文 - 詳細
| RRC ID | 42784 |
|---|---|
| 著者 | Tamaki H, Nakamura H, Nishio A, Nakase H, Ueno S, Uza N, Kido M, Inoue S, Mikami S, Asada M, Kiriya K, Kitamura H, Ohashi S, Fukui T, Kawasaki K, Matsuura M, Ishii Y, Okazaki K, Yodoi J, Chiba T. |
| タイトル | Human thioredoxin-1 ameliorates experimental murine colitis in association with suppressed macrophage inhibitory factor production. |
| ジャーナル | Gastroenterology |
| Abstract |
BACKGROUND & AIMS:Thioredoxin-1 (TRX) is a small multifunctional protein with antioxidative and redox-regulating functions. In this study, we investigated the significance of TRX in patients with inflammatory bowel disease (IBD) and the ability and mechanism to ameliorate experimental colitis. METHODS:Serum TRX and macrophage migration inhibitory factor (MIF) levels were measured in patients with IBD. The effects of TRX were evaluated in a dextran sulfate sodium (DSS)-induced colitis model by comparing TRX-overexpressing transgenic (TRX-TG) and control mice. We further evaluated the effect of recombinant human TRX (rhTRX) administration on DSS-induced colitis and colonic inflammation of interleukin (IL)-10 knockout (IL-10 KO) mice. Colonic inflammation was examined clinically and histologically. Proinflammatory cytokine levels were examined in colonic tissues, and MIF levels were measured in colonic tissues and sera in mice. The effect of TRX on MIF production was also analyzed in vitro. RESULTS:Serum TRX and MIF levels were significantly higher in patients with IBD than normal controls, and TRX levels correlated with disease activity. TRX significantly ameliorated DSS-induced colitis and colonic inflammation of IL-10 KO mice. Increase of tumor necrosis factor-alpha and interferon-gamma in colonic tissues was significantly suppressed in TRX-TG mice compared with wild-type mice. MIF levels in colonic tissues and sera were significantly lower in TRX-TG mice than in wild-type mice, irrespective of DSS administration. Anti-TRX treatment exacerbated DSS-induced colitis. In vitro studies demonstrated that rhTRX suppressed MIF production in human monocyte cells. CONCLUSIONS:TRX might have a potential as a novel therapeutic agent for the treatment of IBD. |
| 巻・号 | 131(4) |
| ページ | 1110-21 |
| 公開日 | 2006-10-1 |
| DOI | 10.1053/j.gastro.2006.08.023 |
| PII | S0016-5085(06)01762-8 |
| PMID | 17030181 |
| MeSH | Animals Anticoagulants Cell Line, Tumor Colitis, Ulcerative / blood Colitis, Ulcerative / chemically induced Colitis, Ulcerative / drug therapy* Colitis, Ulcerative / immunology* Colon / metabolism Crohn Disease / blood Crohn Disease / drug therapy Crohn Disease / immunology Dextran Sulfate Disease Models, Animal Female Gene Expression Humans Immune Sera / pharmacology Interferon-gamma / metabolism Interleukin-10 / genetics Intramolecular Oxidoreductases Leukemia, Monocytic, Acute Macrophage Migration-Inhibitory Factors / blood* Male Mice Mice, Inbred C57BL Mice, Knockout Monocytes / drug effects* Monocytes / immunology Oxidation-Reduction Oxidative Stress / drug effects Oxidative Stress / physiology Recombinant Proteins / immunology Recombinant Proteins / pharmacology Thioredoxins / blood Thioredoxins / genetics Thioredoxins / pharmacology* Tumor Necrosis Factor-alpha / metabolism |
| IF | 17.373 |
| 引用数 | 79 |
| WOS 分野 | GASTROENTEROLOGY & HEPATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | THP-1(RCB1189) |