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Inhalation of Carbon Monoxide Ameliorates TNBS-Induced Colitis in Mice Through the Inhibition of TNF-α Expression

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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.

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Acknowledgments

This work was supported by a Grant-in-Aid for Scientific Research (grant no. 18590694) from the Ministry of Health, Labour and Welfare of Japan.

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Authors and Affiliations

  1. Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Tomohisa Takagi, Yuji Naito, Katsura Mizushima, Satomi Akagiri, Takahiro Suzuki, Ikuhiro Hirata, Tatsushi Omatsu, Osamu Handa, Satoshi Kokura, Hiroshi Ichikawa & Toshikazu Yoshikawa

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  1. Tomohisa Takagi
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  2. Yuji Naito
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  3. Katsura Mizushima
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Correspondence to Yuji Naito.

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Takagi, T., Naito, Y., Mizushima, K. et al. Inhalation of Carbon Monoxide Ameliorates TNBS-Induced Colitis in Mice Through the Inhibition of TNF-α Expression. Dig Dis Sci 55, 2797–2804 (2010). https://doi.org/10.1007/s10620-009-1112-x

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  • DOI: https://doi.org/10.1007/s10620-009-1112-x

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