Kynurenine Attenuates\nUlcerative Colitis Mediated\nby the Aryl Hydrocarbon Receptor

The higher prevalence of ulcerative\ncolitis (UC) and the side effects\nof its therapeutic agents contribute to finding novel treatments.\nThis study aimed to investigate whether kynurenine (KYN), a tryptophan\nmetabolite, has the possibility of alleviating UC and further clarifying\nthe underlying mechanism. The effect of KYN on treating UC was evaluated\nby intestinal pathology, inflammatory cytokines, and tight-junction\nproteins in colitis mice and LPS-stimulated Caco-2 cells. Our results\nrevealed that KYN relieved pathological symptoms of UC, improved intestinal\nbarrier function, enhanced AhR expression, and inhibited NF-κB\nsignaling pathway activation in the colon of colitis mice. Moreover,\nthe improved intestinal barrier function, the decreased inflammasome\nproduction, and the inhibited activation of the NF-κB signaling\npathway by KYN were dependent on AhR in Caco-2 cells. KYN could trigger\nAhR activation, inactivate the NF-κB signaling pathway, and\ninhibit NLRP3 inflammasome production, thus alleviating intestinal\nepithelial barrier dysfunction and reducing intestinal inflammation.\nIn conclusion, the present study reveals that KYN ameliorates UC by\nimproving the intestinal epithelial barrier and activating the AhR-NF-κB-NLRP3\nsignaling pathway, and it can be a promising therapeutic agent and\ndietary supplement for alleviating UC.