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A Role of the Aryl Hydrocarbon Receptor in Attenuation of Colitis

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Abstract

Background and Aims

The aryl hydrocarbon receptor (AhR), which is a member of the basic helix-loop-helix/Per-Arnt-Sim homology superfamily, plays an important role in multiple biological functions, and AhR knockout (AhR KO) animals suffer from a variety of organ disorders including a decline in the efficacy of their immune system. In addition, AhR activation is known to aid the maintenance of homeostasis in vivo. In this study, we investigated whether AhR is functionally associated with intestinal immunity.

Methods and Results

In in vivo experiments, it was found that dextran sodium sulfate (DSS)-evoked colitis was more severe in AhR KO mice than in C57BL/6J wild type mice. It was also revealed that the administration of DSS increased the expression levels of AhR and CYP1A1 mRNA in the colon epithelium. In addition, oral administration of β-naphthoflavone (βNF), a non-toxic agonist of AhR, suppressed the pathogenesis of DSS-induced colitis. βNF also attenuated DSS-induced colitis. In cell culture experiments, downregulation of AhR in human colon carcinoma SW480 cells enhanced the inflammatory responses evoked by lipopolysaccharide (LPS), and furthermore, AhR activation attenuated LPS-induced inflammatory responses, suggesting that AhR expressing intestinal epithelial cells are involved in the prevention of colitis.

Conclusions

Our findings about the potential role of AhR activators in epithelial immune regulation aid our understanding of mucosal homeostasis and inflammatory bowl disease (IBD) and suggest that AhR activation has therapeutic value for the treatment of IBD.

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Acknowledgments

This work was supported, in part, by a grant for the Global COE Program “Global Center of Excellence for Education and Research on Signal Transduction Medicine in the Coming Generation” from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (M.Y., T.A). This work was also supported by a grant for the Education Program for Specialized Clinicians as part of the Support Program for Improving Graduate School Education from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (K.F.). This work was partly supported by a grant from the program ‘Young researchers training program for promoting innovation’ of Special Coordination Fund for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (S.N., T.A.).

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Chuo-ku, Kusunoki-cho, Kobe, Hyogo, 650-0017, Japan

    Keisuke Furumatsu, Shin Nishiumi, Yuki Kawano, Makoto Ooi, Tomoo Yoshie, Yuuki Shiomi, Hiromu Kutsumi, Takeshi Azuma & Masaru Yoshida

  2. The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, Kobe, Japan

    Shin Nishiumi & Masaru Yoshida

  3. Division of Metabolomics Research, Kobe University Graduate School of Medicine, Kobe, Japan

    Masaru Yoshida

  4. Department of Agrobioscience, Kobe University Graduate School of Agricultural Science, Kobe, Japan

    Hitoshi Ashida

  5. Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Japan

    Yoshiaki Fujii-Kuriyama

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  1. Keisuke Furumatsu
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  2. Shin Nishiumi
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Correspondence to Masaru Yoshida.

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Furumatsu, K., Nishiumi, S., Kawano, Y. et al. A Role of the Aryl Hydrocarbon Receptor in Attenuation of Colitis. Dig Dis Sci 56, 2532–2544 (2011). https://doi.org/10.1007/s10620-011-1643-9

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  • DOI: https://doi.org/10.1007/s10620-011-1643-9

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