Finally, the correlation between NOR-mediated activation of AhR, repression of glycolysis, regulation of NAD<sup>+</sup>/SIRT1/SUV39H1/H3K9me3 signals, induction of Treg cells, and remission of colitis was confirmed in mice with DSS-induced colitis by using CH223191 and HK2 plasmid.
Further, the increase of both MLC phosphorylation and MLCK expression in the mice with DSS-induced colitis was also significantly inhibited by FICZ induced AhR activation.
Our data show that AhR activation by FICZ ameliorated colonic inflammation, decreased IL-6 and claudin-2 expression, and maintained intestinal barrier function in a mouse model of dextran sulphate sodium (DSS)-induced colitis.
Finally, correlations between activation of AhR and attenuation of colitis, inhibition of NLRP3 inflammasome activation and up-regulation of Nrf2 level in colons were validated in mice with TNBS-induced colitis.
These results suggested that AhR deficiency resulted in increased susceptibility to colitis, whereas activation of AhR by FICZ could ameliorate DSS‑induced colitis via the MK2/p‑MK2/TTP pathway.
The microbiota from CARD9 mice fails to metabolize tryptophan leading to defective AhR activation which contributes to the susceptibility of mice to colitis by decreased interleukin 22 production.
Furthermore, Ahr-expressing Tregs had enhanced in vivo suppressive activity compared with Tregs lacking Ahr expression in a T cell transfer model of 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.
Attenuation of the AhR receptor expression resulted in a protective effect during DSS-induced colitis, while the absence of AhR exacerbated the disease.
This study investigated whether the activation of the AhR pathway affects dextran sodium sulfate (DSS)-induced colitis, an ulcerative colitis-like model, in mice.