Aryl Hydrocarbon Receptor Activation Modulates Intestinal Epithelial Barrier Function by Maintaining Tight Junction Integrity

• Published in: International journal of biological sciences Vol. 14; no. 1; pp. 69 - 77
• Main Authors: Yu, Min, Wang, Qimeng, Ma, Yuanhang, Li, Liangzi, Yu, Kun, Zhang, Zhicao, Chen, Guoqing, Li, Xiangsheng, Xiao, Weidong, Xu, Pengyuan, Yang, Hua
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 01.01.2018; Ivyspring International Publisher
• Subjects: Activation; Animals; Aromatic compounds; Barriers; Blotting, Western; Caco-2 Cells; Carbazole; Chemical compounds; Colitis; Colitis - metabolism; Dextran; Dextran Sulfate - pharmacology; Fluorescent Antibody Technique; Homeostasis; Humans; Hydrocarbons; Immunohistochemistry; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - metabolism; Interferon; Interferon-gamma - metabolism; Intestinal Mucosa - metabolism; Intestine; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Mucosa; Myosin Light Chains - metabolism; Myosin-light-chain kinase; NF-κB protein; Pharmacology; Phosphorylation; Phosphorylation - drug effects; Phosphorylation - genetics; Receptor mechanisms; Receptors, Aryl Hydrocarbon - genetics; Receptors, Aryl Hydrocarbon - metabolism; Research Paper; Signal transduction; Signal Transduction - drug effects; Signal Transduction - genetics; Signaling; Small intestine; Sodium; Tight Junctions - metabolism; Transcription factors; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; α-Interferon; γ-Interferon; Aryl hydrocarbon receptor; myosin light chain; intestinal barrier function; inflammatory bowel disease; tight junction
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.22259

Activation of Aryl hydrocarbon receptor (AhR) is involved in the control of intestinal mucosal homeostasis. Intestinal barrier dysfunction contributes to the development of many intestinal diseases, such as inflammatory bowel disease (IBD). In this study, we investigated the mechanisms of AhR activation in the maintenance of intestinal barrier function. Adult C57BL/6 mice were treated with dextran sulphate sodium (DSS) for 7 days, with or without 6-Formylindolo(3,2-b)carbazole (FICZ), a ligand of AhR. We found that AhR activation by FICZ attenuated the decreased TJ protein expression in the colonic mucosa of the DSS-induced mice. 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. For experiments, Caco-2 cells were treated with tumour necrosis factor alpha (TNF-α)/interferon gamma (IFN-γ) for 48 h, with or without FICZ. AhR activation prevented TNF-α/IFN-γ-induced decrease in TER and morphological disruption of the TJs in Caco-2 monolayers. It also inhibited TNF-α/IFN-γ-induced increase in MLCK expression and MLC phosphorylation by suppression of NF-κB p65 signaling pathway. Thus, AhR-activating factors might have potential as therapeutic agents for the treatment of patients with IBD.