Deoxynivalenol triggers pyroptosis in intestinal epithelial cells via NLRP3 inflammasome activation mediated by the TLR4-NF-κB/p38 MAPK signaling pathway.

Deoxynivalenol (DON), a common food contaminant, induces pyroptosis in intestinal epithelial cells by activating the NLRP3 inflammasome, though the mechanism remains unclear. This study utilized 32 male Kunming mice and rat small intestinal epithelial (IEC-6) cells treated with DON at concentrations of 0-4.8 mg/kg (7 days) and 0-1 μM (24 h), respectively. Results demonstrated that DON induced intestinal epithelial damage and activated the NLRP3 inflammasome, leading to pyroptosis, while also activating the TLR4-NF-κB/p38 MAPK pathway. Pretreatment with PDTC (NF-κB inhibitor) and SB203580 (p38 MAPK inhibitor) suppressed NLRP3 inflammasome priming and activation, respectively, reducing pyroptosis in IEC-6 cells. TLR4 inhibition with TLR4-IN-C34 confirmed that TLR4 acts as an upstream regulator controlling both NF-κB and p38 MAPK signaling, thus inhibiting NLRP3 inflammasome activation and alleviating pyroptosis. Thus, DON activates the TLR4-NF-κB/p38 MAPK pathway, triggering NLRP3 inflammasome priming and activation, which ultimately leads to pyroptosis in intestinal epithelial cells.