A role of the aryl hydrocarbon receptor in attenuation of colitis.
Dig Dis Sci
; 56(9): 2532-44, 2011 Sep.
Article
en En
| MEDLINE
| ID: mdl-21374063
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 ANDRESULTS:
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 ß-naphthoflavone (ßNF), a non-toxic agonist of AhR, suppressed the pathogenesis of DSS-induced colitis. ßNF 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Receptores de Hidrocarburo de Aril
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Colitis
Límite:
Animals
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Female
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Humans
Idioma:
En
Año:
2011
Tipo del documento:
Article