title: Inhalation of carbon monoxide ameliorates TNBS-induced colitis in mice through the inhibition of TNF-α expression.
abstract: BACKGROUND
  Carbon monoxide (CO), long considered a toxic gas, has recently been shown to mediate anti-inflammatory effects in various animal models. The aim of this study was to investigate whether the inhalation of CO ameliorated 2,4,6-trinitrobenzine sulfonic acid (TNBS)-induced colitis in mice.
  
  
  METHODS
  The CO treatment group was exposed to CO gas at a concentration of 200 ppm in a closed cage starting on the day when TNBS was administered and throughout the remaining study period. The distal colon was removed, and ulcerative lesions were subsequently evaluated with macroscopic damage scores. Furthermore, thiobarbituric acid (TBA)-reactive substances and tissue-associated myeloperoxidase (MPO) activity in colonic mucosa were measured as indices of lipid peroxidation and neutrophil infiltration. The expressions of TNF-α in colonic mucosa were also measured by enzyme-linked immunosorbent assay. In additional experiments in vitro, CD4(+) T cells isolated from the spleen were stimulated with anti-CD3/CD28 Ab, and the cells and supernatants were collected and evaluated for TNF-α expression.
  
  
  RESULTS
  The increased colonic damage after TNBS administration was significantly inhibited by the treatment with CO. Furthermore, CO significantly inhibited the increases in TBA-reactive substances, MPO activity and TNF-α production in colonic mucosa after the induction of TNBS colitis. In CD4(+) T cells isolated from mice treated with CO inhalation, the production of TNF-α was significantly inhibited.
  
  
  CONCLUSIONS
  The inhalation of CO protected mice from developing intestinal inflammation. Based on these data, the beneficial effects of CO in a murine colitis model may be attributed to its anti-inflammatory properties.
authors.affiliation: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Takagi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Katsura
authors.initials: K
authors.lastname: Mizushima
authors.forename: Satomi
authors.initials: S
authors.lastname: Akagiri
authors.forename: Takahiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Ikuhiro
authors.initials: I
authors.lastname: Hirata
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Omatsu
authors.forename: Osamu
authors.initials: O
authors.lastname: Handa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology; D002248:Carbon Monoxide / Q000494:pharmacology*; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D018106:CD28 Antigens; D017252:CD3 Complex; D012333:RNA, Messenger; D017392:Thiobarbituric Acid Reactive Substances; D014409:Tumor Necrosis Factor-alpha; D002248:Carbon Monoxide; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase