β-defensin 118 attenuates inflammation and injury of intestinal epithelial cells upon enterotoxigenic Escherichia coli challenge

Background: Antimicrobial peptides including various defensins have been attracting considerable research interest worldwide, as they have potential to substitute for antibiotics. Moreover, AMPs also have immunomodulatory activity. In this study, we explored the role and its potential mechanisms of beta-defensin 118 (DEFB118) in alleviating inflammation and injury of IPEC-J2 cells (porcine jejunum epithelial cell line) upon the enterotoxigenic Escherichia coli (ETEC) challenge. Results: The porcine jejunum epithelial cell line (IPEC-J2) pretreated with or without DEFB118 (25 mu g/mL) were challenged by ETEC (1x10(6) CFU) or culture medium. We showed that DEFB118 pretreatment significantly increased the cell viability (P<0.05) and decreased the expressions of inflammatory cytokines such as the interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in IPEC-J2 cells exposure to ETEC (P<0.05). Interestingly, DEFB118 pretreatment significantly elevated the abundance of the major tight-junction protein zonula occludens-1 (ZO-1), but decreased the number of apoptotic cells upon ETEC challenge (P<0.05). The expression of caspase 3, caspase 8, and caspase 9 were downregulated by DEFB118 in the IPEC-J2 cells exposure to ETEC (P<0.05). Importantly, DEFB118 suppressed two critical inflammation-associated signaling proteins, nuclear factor-kappa-B inhibitor alpha (I kappa B-alpha) and nuclear factor-kappaB (NF-kappa B) in the ETEC-challenged IPEC-J2 cells. Conclusions: DEFB118 can alleviate ETEC-induced inflammation in IPEC-J2 cells through inhibition of the NF-kappa B signaling pathway, resulting in reduced secretion of inflammatory cytokines and decreased cell apoptosis. Therefore, DEFB118 can act as a novel anti-inflammatory agent.

Automated summary

In this study, the researchers investigated the role and mechanism of DEFB118 in alleviating inflammation and cell injury caused by ETEC in IPEC-J2 cells. They found that DEFB118 pretreatment increased cell viability, reduced expression of inflammatory cytokines, elevated the abundance of a tight-junction protein, and decreased the number of apoptotic cells. DEFB118 also downregulated the expression of caspase proteins and suppressed inflammation-associated signaling proteins in ETEC-challenged IPEC-J2 cells. This study suggests that DEFB118 can act as a novel anti-inflammatory agent.