Sodium butyrate improves porcine host defense peptide expression and relieves the inflammatory response upon toll-like receptor 2 activation and histone deacetylase inhibition in porcine kidney cells

Abstract

Host defense peptides (HDPs) are an important component of the innate immune system and possess direct antimicrobial and immunomodulatory activities. Dietary regulation of HDPs synthesis has emerged as a novel non-antibiotic approach to combat pathogen infection. There are species- and tissue-dependent characteristics of the regulation and mechanism of HDPs. In this study, we investigated whether the histone deacetylase inhibitor (HDACi) sodium butyrate (NaB) could induce HDP expression and the mechanism underlying NaB-regulated HDP expression in PK-15 cells. Our results revealed that NaB augmented HDP expression in PK-15 cells, including porcine β-defensin 3 (pBD3), epididymis protein 2 splicing variant C (pEP2C), pBD128, pBD123, and pBD115, but no inflammatory response occurred. Inhibition of HDAC activity was not sufficient to induce the expression of pBD3 and pEP2C in comparisons of NaB and another HDACi, trichostatin A (TSA). Concomitantly, NF-κB activation was involved in the induction of HDP expression by NaB. MAPK pathway inhibition also prevented pBD3 and pEP2C induction by NaB. Furthermore, NaB could still promote pBD3 and pEP2C expression and inhibit IL-6 production in the presence of the toll-like receptor 2 (TLR2) ligand peptidoglycan. Moreover, TLR2 could be activated by both NaB and peptidoglycan, and blocking TLR2 expression suppressed HDP induction. Finally, we further showed that increased pBD3 could decrease cytokine interleukin-18 (IL-18) and increase porcine claudin 15 (pCLDN15) contents, suggesting an immunoregulatory function of pBD3. In conclusion, this work paves the way for using HDACi-NaB to induce porcine kidney defense peptides while limiting the deleterious risk of an inflammatory response.

Swine-Derived Probiotic Lactobacillus plantarum Inhibits Growth and Adhesion of Enterotoxigenic Escherichia coli and Mediates Host Defense

“…Upregulation of pBD2 in response to L. plantarum ZLP001 likely inhibited pathogenic bacteria in our study, as reported previously that pBD2 protects against a wide range of pathogenic bacteria in vitro ( Veldhuizen et al, 2007 ; Zhang et al, 2011 ; Deng et al, 2013 ). pBD3 exhibits not only profound antimicrobial properties, but also strong immunoregulatory ability by regulating the expression of the proinflammatory cytokine IL-8 ( Dou et al, 2017 ). In the present study, pBD3 mRNA expression was considerably increased only at the highest concentration of L. plantarum ZLP001, which was inconsistent with another report of high pBD3 expression at 10 7 and 10 8 CFU/mL ( Liu et al, 2017 ).…”

WITHDRAWN: Maternal dietary resveratrol alleviates weaning-associated intestinal inflammation and diarrhea in porcine offspring by altering intestinal gene expression and microbiota

“…Butyrate, an important energy source for intestinal epithelial cells, has been shown to stimulate growth of small intestinal epithelium and maintain intestinal homeostasis. The effects of butyrate on oxidative stress, inflammation [39], and intestinal barrier function [40] have been described, particularly its activities in promoting gut health both in vitro [41] and in vivo [42]. In addition, previous studies reported that butyrate decreased diarrhea incidence in post-weaning piglets [42] and congenital chloride diarrhea children [43].…”

TLR2/4-mediated NF-κB pathway combined with the histone modification regulates β-defensins and interleukins expression by sodium phenyl butyrate in porcine intestinal epithelial cells

“…Each sample reaction was run in duplicate on the same plate. The gene-specific primers are presented in Table 1 (14–16). The mRNA expression levels were determined using the 2 −ΔΔCt method with β-actin as a reference.…”