Effects of Clostridium perfringens beta2 toxin on apoptosis, inflammation, and barrier function of intestinal porcine epithelial cells

Clostridium perfringens beta2 (CPB2) toxin is an important virulence factor that causes enteric diseases in both humans and animals. To investigate the underlying mechanism in CPB2-induced inflammation and damage in the small intestinal epithelium, intestinal porcine epithelial cells (IPEC-J2) were treated with recombinant CPB2 (rCPB2) toxin. The results showed that IPEC-J2 cell viability was decreased by rCPB2 toxin treatment in a dose- and time-dependent manner. Analysis of cell morphology and Annexin V-FTIC/PI staining revealed that rCPB2 toxin induces cell apoptosis. Indeed, the expression of caspase-3, caspase-8, and caspase-9 was significantly increased at both the mRNA and protein levels in IPEC-J2 cells treated with rCPB2 toxin. The caspase-3 inhibitor Ac-DEVD-CHO reduced rCPB2 toxin-induced cell apoptosis. Moreover, exposure to the toxin increased the expression of interleukin (IL)-6, IL-7, IL-12, and IL-1β, while decreasing that of transforming growth factor beta 1 (TGFβ1). Additionally, rCPB2 toxin treatment also induced intestinal barrier dysfunction, as evidenced by the degradation of zonula occludens (ZO)-1, claudin-1, and E-cadherin, as well as an increase in paracellular permeability. Overall, the results indicated that rCPB2 toxin induces apoptosis and inflammation, in addition to impairing intestinal barrier function in IPEC-J2 cells. Our findings provide a foundation to better understand the pathogenesis of C. perfringens infection and inform strategies to effectively prevent and treat C. perfringens-induced enteric diseases.