mTOR-Mediated Autophagy Regulates Fumonisin B 1 -Induced Intestinal Inflammation via Pyroptosis In Vivo and In Vitro.

Fumonisin B 1 (FB 1 ) is a fungal metabolite, which has an incremental detection rate in grains and feed worldwide. The nucleotide-binding oligomerization domain-like pyrin domain containing protein 3 (NLRP3) inflammasome is a critical element in pyroptosis activation, which participates in regulating enteritis. Meanwhile, autophagy is also engaged in intestinal inflammation. However, the function of pyroptosis and autophagy in FB 1 -mediated enterotoxicity remains unclear. In this study, we explored the effects of FB 1 on enteritis and the underlying mechanism in vivo and in vitro. Our data showed that FB 1 exposure damaged the intestinal epithelium and promoted the secretion of inflammatory cytokines. Meanwhile, FB 1 exposure significantly upregulated the expression of pyroptosis-related genes. Then, MCC950, an inhibitor of NLRP3, significantly blocked FB 1 -induced pyroptosis in IPEC-J2 cells. In addition, FB 1 treatment elevated the levels of autophagy. Moreover, the phosphorylation of the mammalian target of rapamycin (mTOR), an upstream protein of the autophagy pathway, was inhibited by FB 1 exposure. Notably, rapamycin, an inhibitor of mTOR, instead of MHY1485, an agonist of mTOR, could ameliorate FB 1 -induced intestinal inflammatory injury and inhibit the upregulation of pyroptosis-related genes. In summary, we demonstrated that autophagy exhibited a protective effect against NLRP3 inflammasome-dependent pyroptosis on FB 1 -induced enteritis. Our data clarify a favorable protective role for the activation of autophagy in FB 1 poisoning.