BackgroundHost defense peptides (HDPs) possess direct antibacterial, antineoplastic, and immunomodulatory abilities, playing a vital role in innate immunity. Dietary-regulated HDP holds immense potential as a novel pathway for preventing infection.ObjectiveIn this study, we examined the regulation mechanism of HDPs (pEP2C, pBD-1, and pBD-3) and cytokines (IL-8 and IL-18) expression by sodium phenylbutyrate (PBA).DesignThe effects of PBA on HDP induction and the mechanism involved were studied in porcine intestinal epithelial cell lines (IPEC J2).ResultsIn this study, the results showed that HDPs (pEP2C, pBD-1, and pBD-3) and cytokines (IL-8 and IL-18) expression was increased significantly upon stimulation with PBA in IPEC J2 cells. Furthermore, toll-like receptor 2 (TLR2) and TLR4 were required for the PBA-mediated upregulation of the HDPs. This process occurred and further activated the NF-κB pathway via the phosphorylation of p65 and an IκB α synthesis delay. Meanwhile, histone deacetylase (HDAC) inhibition and an increased phosphorylation of histone H3 on serine S10 also occurred in PBA-induced HDP expression independently with TLR2 and TLR4. Furthermore, p38-MAPK suppressed PBA-induced pEP2C, pBD-1 pBD-3, IL-8, and IL-18 expression, but ERK1/2 failed to abolish the regulation of pBD-3, IL-8, and IL-18. Moreover, epidermal growth factor receptor (EGFR) is involved in PBA-mediated HDP regulation.ConclusionsWe concluded that PBA induced HDP and cytokine increases but did not cause an excessive pro-inflammatory response, which proceeded through the TLR2 and TLR4-NF-κB pathway and histone modification in IPEC J2 cells.

This study aimed to determine the effects of the antimicrobial peptide WK3, as an alternative to antibiotics, on diarrheic piglets. Before treatment, all pigs were orally challenged with 10 8 CFU/ml enterotoxigenic Escherichia coli (ETEC) K88 for 3 days. Piglets were randomly divided into 3 treatments of eight piglets each, namely, the control treatment, antibiotic treatment and antimicrobial peptide treatment. The experimental results show that the addition of the antibacterial peptide WK3 to the diet can significantly reduce the chance of diarrhea. Compared with the CON group, average daily gain (ADG) and average daily feed intake (ADFI) of the WK3 group (P < 0.05) increased. Compared with that with the control treatment and antibiotic treatment, the level of GSH-Px in the jejunum significantly increased (P < 0.05) with WK3 supplementation. The numbers of bacteria, Lactobacillus spp. (P < 0.01) and Bifidobacteria spp. (P < 0.01), were higher in the WK3 group, but Enterobacterium spp. in digesta of the cecum were depleted (P < 0.01). The WK3 group decreased the expression levels of the inflammatory factors IL-1α (P < 0.05) and TLR-4 (P < 0.01) in the jejunal mucosa contrast to the control treatment.

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