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

ABSTRACT: Background:Host 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. Objective:In 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). Design:The effects of PBA on HDP induction and the mechanism involved were studied in porcine intestinal epithelial cell lines (IPEC J2). Results:In 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-?B pathway via the phosphorylation of p65 and an I?B ? 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. Conclusions:We 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-?B pathway and histone modification in IPEC J2 cells.

SUBMITTER: Dou X

PROVIDER: S-EPMC6294838 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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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.

Dou Xiujing X Han Junlan J Ma Qiuyuan Q Cheng Baojing B Shan Anshan A Gao Nan N Yang Yu Y

Food & nutrition research 20181206

<h4>Background</h4>Host 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.<h4>Objective</h4>In 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).<h4>Design</h4>The effects of PBA on HDP induction and the mechani ...[more]

PMID: 30574051

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Dataset Information

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

Publications

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.

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