AHR activation relieves deoxynivalenol-induced disruption of porcine intestinal epithelial barrier functions

Mycotoxins are ubiquitous natural pollutants that pose a serious threat to public health. Deoxynivalenol (DON) as one of the most prominent mycotoxins has a noticeable adverse effect on intestinal barrier function, which depends on the intestinal barrier integrity. However, the potential mechanisms and effective therapeutic strategies remain unclear. Aryl hydrocarbon receptor (AHR) has been implicated in the modulation of intestinal barrier function and inflammation. The study aims to investigate the unique role of AHR in mediating DON-induced intestinal epithelial barrier function. In the current study, we revealed that DON triggered mitochondrial structural damage and functional impairment, leading to oxidative stress and apoptosis in porcine jejunal epithelial cells (IPEC-J2). DON altered the integrity of IPEC-J2 cells by disrupting the distribution and function of tight junction proteins. Additionally, DON activated TNF-α/NF-κB/MLCK signaling pathway, thereby eliciting inflammatory response. Notably, DON inhibited AHR nuclear translocation and attenuated xenobiotic response element promoter activity and its target genes. However, overexpression of AHR mitigated DON-induced disruption of intestinal epithelial barrier functions by suppressing TNF-α/NF-κB/MLCK pathway in IPEC-J2 cells. Our findings indicate that AHR regulates intestinal epithelial barrier function and therefore is a novel therapeutic molecule for intestinal disorders. DON causes structural damage to IPEC-J2 cells and induces disruption of porcine intestinal epithelial barrier functions by targeting AHR-mediated TNF-α/NF-κB/MLCK signaling pathway. The ability to regulate AHR activity holds potential in treating DON-induced intestinal disease. • DON disrupts porcine intestinal epithelial barrier functions. • DON causes inflammatory response by activating TNF-α/NF-κB/MLCK pathway. • DON directly binds to AHR and thus inhibits the activation of classic AHR pathway. • AHR overexpression relives DON-induced intestinal epithelial barrier dysfunction.