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

  • Xiujing Dou Northeast Agriculture University
  • Junlan Han
  • Qiuyuan Ma
  • Baojing Cheng
  • Anshan Shan
  • Nan Gao
  • Yu Yang
Keywords: Sodium phenylbutyrate; β-defensins; Inflammatory cytokines; Signaling pathway


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-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.

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-κB pathway and histone modification in IPEC J2 cells.


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How to Cite
Dou X, Han J, Ma Q, Cheng B, Shan A, Gao N, Yang Y. 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. fnr [Internet]. 2018Dec.6 [cited 2018Dec.19];620. Available from:
Original Articles