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 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.