Different Lipopolysaccharide Branched-Chain Amino Acids Modulate Porcine Intestinal Endogenous β‑Defensin Expression through the Sirt1/ERK/90RSK Pathway

Nutritional induction of endogenous antimicrobial peptide expression is considered a promising approach to inhibit the outgrowth and infection of pathogenic microbes in mammals. The present study investigated possible regulation of porcine epithelial β-defensins in response to branched-chain amino a...

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Published in:Journal of agricultural and food chemistry 2016-05, Vol.64 (17), p.3371-3379
Main Authors: Ren, Man, Zhang, Shihai, Liu, Xutong, Li, Shenghe, Mao, Xiangbing, Zeng, Xiangfang, Qiao, Shiyan
Format: Article
Language:English
Subjects:
Amino Acids, Branched-Chain - chemistry
Amino Acids, Branched-Chain - pharmacology
Animals
beta-Defensins - metabolism
Intestines - drug effects
Intestines - metabolism
Lipopolysaccharides - chemistry
Male
MAP Kinase Signaling System
Sirtuin 1 - metabolism
Swine
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Summary:Nutritional induction of endogenous antimicrobial peptide expression is considered a promising approach to inhibit the outgrowth and infection of pathogenic microbes in mammals. The present study investigated possible regulation of porcine epithelial β-defensins in response to branched-chain amino acids (BCAA) in vivo and in vitro. BCAA treatment increased relative mRNA expression of jejunal and ileal β-defensins in weaned piglets. In IPEC-J2 cells, isoleucine, leucine, and valine could stimulate β-defensin expression, possibly associated with stimulation of ERK1/2 phosphorylation. Inhibition of Sirt1 and ERK completely blocked the activation of ERK and 90RSK protein by isoleucine, simultaneously decreasing defensin expression. BCAA stimulate expression of porcine intestinal epithelial β-defensins with isoleucine the most, potent possibly through activation of the Sirt1/ERK/90RSK signaling pathway. The β-defensins regulation of lipopolysaccharide was related with an ERK-independent pathway. BCAA modulation of endogenous defensin might be a promising approach to enhance disease resistance and intestinal health in young animals and children.
ISSN:0021-8561
1520-5118
DOI:10.1021/acs.jafc.6b00968