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Kynurenine Attenuates Ulcerative Colitis Mediated by the Aryl Hydrocarbon Receptor

文献类型: 外文期刊

作者: Wang, Caihong 1 ; Xu, Qihao 1 ; Wei, Chaozhi 3 ; Hu, Qinglian 1 ; Xiao, Yingping 2 ; Jin, Yuanxiang 1 ;

作者机构: 1.Zhejiang Univ Technol, Coll Biotechnol & Bioengn, Hangzhou 310032, Peoples R China

2.Zhejiang Acad Agr Sci, Inst Agroprod Safety & Nutr, State Key Lab Managing Biot & Chem Threats Qual &, Hangzhou 310021, Peoples R China

3.Xianghu Lab, Hangzhou 311231, Peoples R China

关键词: kynurenine; AhR; intestinal epithelial barrier; ulcerative colitis; NF-kappa B signaling pathway

期刊名称:JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY ( 影响因子:6.2; 五年影响因子:6.4 )

ISSN: 0021-8561

年卷期: 2024 年 72 卷 38 期

页码:

收录情况: SCI

摘要: The higher prevalence of ulcerative colitis (UC) and the side effects of its therapeutic agents contribute to finding novel treatments. This study aimed to investigate whether kynurenine (KYN), a tryptophan metabolite, has the possibility of alleviating UC and further clarifying the underlying mechanism. The effect of KYN on treating UC was evaluated by intestinal pathology, inflammatory cytokines, and tight-junction proteins in colitis mice and LPS-stimulated Caco-2 cells. Our results revealed that KYN relieved pathological symptoms of UC, improved intestinal barrier function, enhanced AhR expression, and inhibited NF-kappa B signaling pathway activation in the colon of colitis mice. Moreover, the improved intestinal barrier function, the decreased inflammasome production, and the inhibited activation of the NF-kappa B signaling pathway by KYN were dependent on AhR in Caco-2 cells. KYN could trigger AhR activation, inactivate the NF-kappa B signaling pathway, and inhibit NLRP3 inflammasome production, thus alleviating intestinal epithelial barrier dysfunction and reducing intestinal inflammation. In conclusion, the present study reveals that KYN ameliorates UC by improving the intestinal epithelial barrier and activating the AhR-NF-kappa B-NLRP3 signaling pathway, and it can be a promising therapeutic agent and dietary supplement for alleviating UC.

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