Aryl hydrocarbon receptor inhibits inflammation in DSS‑induced colitis via the MK2/p‑MK2/TTP pathway

Wang,Qimeng; Yang,Kunqiu; Han,Bin; Sheng,Baifa; Yin,Jiuheng; Pu,Aimin; Li,Liangzi; Sun,Lihua; Yu,Min; Qiu,Yuan; Xiao,Weidong; Yang,Hua

doi:10.3892/ijmm.2017.3262

Aryl hydrocarbon receptor inhibits inflammation in DSS‑induced colitis via the MK2/p‑MK2/TTP pathway

Authors:
- Qimeng Wang
- Kunqiu Yang
- Bin Han
- Baifa Sheng
- Jiuheng Yin
- Aimin Pu
- Liangzi Li
- Lihua Sun
- Min Yu
- Yuan Qiu
- Weidong Xiao
- Hua Yang
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Affiliations: Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China
Published online on: November 17, 2017 https://doi.org/10.3892/ijmm.2017.3262
Pages: 868-876
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The pathogenesis of inflammatory bowel disease (IBD) is believed to be associated with the abnormal expression of inflammatory factors. The aryl hydrocarbon receptor (AhR) is a ligand‑dependent transcription factor, which can suppress the inflammatory response and attenuate experimental colitis. However, the detailed mechanism underlying the effects of AhR remains unclear. The present study investigated the role of AhR in the pathogenesis of IBD. Colitis was induced in mice by administration of 3% dextran sulphate sodium (DSS) for 7 days. The mice were also administered injections of the AhR agonist, 6‑formylindolo(3,2‑b)carbazole (FICZ), starting 2 days after the first administration of DSS. Furthermore, LoVo cells were treated with lipopolysaccharide (LPS) in the presence or absence of FICZ for 8 h. The protein expression levels of AhR, cytochrome P450 1A1 (CYP1A1) and tristetraprolin (TTP) were assessed by western blotting and immunofluorescence, whereas mRNA expression levels were assessed by reverse transcription‑quantitative polymerase chain reaction. The results indicated that injection of mice with FICZ significantly attenuated DSS‑induced colitis; in addition, the expression levels of inflammatory cytokines were markedly downregulated. Conversely, the expression levels of AhR and TTP were upregulated. In addition, mice in the AhR‑knockout + DSS group exhibited elevated inflammatory cytokine production and developed more severe colitis. In LoVo cells, incubation with FICZ decreased the expression levels of inflammatory cytokines, whereas AhR and TTP expression was increased. In addition, the levels of phosphorylated‑mitogen‑activated protein kinase‑activated protein kinase 2 (p‑MK2) were decreased. 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.

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