title: Human thioredoxin-1 ameliorates experimental murine colitis in association with suppressed macrophage inhibitory factor production.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tamaki
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Nishio
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakase
authors.forename: Satoru
authors.initials: S
authors.lastname: Ueno
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Uza
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kido
authors.forename: Satoko
authors.initials: S
authors.lastname: Inoue
authors.forename: Sakae
authors.initials: S
authors.lastname: Mikami
authors.forename: Masanori
authors.initials: M
authors.lastname: Asada
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kiriya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitamura
authors.forename: Shinya
authors.initials: S
authors.lastname: Ohashi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fukui
authors.forename: Kimio
authors.initials: K
authors.lastname: Kawasaki
authors.forename: Minoru
authors.initials: M
authors.lastname: Matsuura
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ishii
authors.forename: Kazuichi
authors.initials: K
authors.lastname: Okazaki
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
mesh_terms: D000818:Animals; D000925:Anticoagulants; D045744:Cell Line, Tumor; D003093:Colitis, Ulcerative / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D003106:Colon / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics; D019746:Intramolecular Oxidoreductases; D007948:Leukemia, Monocytic, Acute; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D013879:Thioredoxins / Q000097:blood / Q000235:genetics / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D007106:Immune Sera; D008263:Macrophage Migration-Inhibitory Factors; D011994:Recombinant Proteins; C491203:TXN protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013879:Thioredoxins; D007371:Interferon-gamma; D016264:Dextran Sulfate; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse