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01.09.2011 | Original Article

A Role of the Aryl Hydrocarbon Receptor in Attenuation of Colitis

verfasst von: Keisuke Furumatsu, Shin Nishiumi, Yuki Kawano, Makoto Ooi, Tomoo Yoshie, Yuuki Shiomi, Hiromu Kutsumi, Hitoshi Ashida, Yoshiaki Fujii-Kuriyama, Takeshi Azuma, Masaru Yoshida

Erschienen in: Digestive Diseases and Sciences | Ausgabe 9/2011

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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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Titel: A Role of the Aryl Hydrocarbon Receptor in Attenuation of Colitis
verfasst von: Keisuke Furumatsu
Shin Nishiumi
Yuki Kawano
Makoto Ooi
Tomoo Yoshie
Yuuki Shiomi
Hiromu Kutsumi
Hitoshi Ashida
Yoshiaki Fujii-Kuriyama
Takeshi Azuma
Masaru Yoshida
Publikationsdatum: 01.09.2011
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 9/2011
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-011-1643-9

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A Role of the Aryl Hydrocarbon Receptor in Attenuation of Colitis