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

Abstract

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.

Branched Chain Amino Acids: Beyond Nutrition Metabolism

“…For example, glutamine, arginine, and threonine could improve integrity of tight junctions, cell migration, anti-oxidative responses, and mucosal barrier functions in the intestine [ 74 ]. Likewise, BCAAs also act as a regulator to promote intestinal development, nutrient transporters, and immune-related function and then improve gut health [ 75 , 76 , 77 ]. However, most of the studies focus on the Leu functions but not Val or Ile in the intestine.…”

“…BCAAs may enhance disease resistance and intestinal health through modulation of endogenous defensin in young animals and children. Ren et al [ 76 ] investigated the mRNA expression of porcine epithelial β-defensins in response to BCAAs. The results indicated that BCAAs treatment increased the expression of β-defensins in jejunum and ileum of weaned piglets, and the similar stimulate effect of BCAAs on β-defensin expression was found in IPEC-J2 cells.…”

l-Isoleucine Administration Alleviates Rotavirus Infection and Immune Response in the Weaned Piglet Model

“…Isoleucine is a kind of branched chain amino acid, which is essential for some physiological functions of humans and pigs ( 7 , 9 – 11 ). Burns ( 9 ) has shown that isoleucine will specifically be incorporated into proteins of immune cells, such as lymphocytes, eosinophils, and neutrophils.…”

Structural modeling and mRNA expression of epididymal β‐defensins in GnRH immunized boars: A model for secondary hypogonadism in man

“…The use of pigs as an animal model for translational research focusing on β‐defensins and infectious diseases is growing (Alizadeh et al, ; Bao et al, ; Liu et al, ; Ren et al, ; Tang et al, ; X. Yang et al, ). The messenger RNA (mRNA) expression of thirteen different porcine β‐defensins has been described in several tissues (G. Zhang et al, ; Sang, Patil, Zhang, Ross, & Blecha, ) and, with regard to the transcriptomics of the swine epididymis, seven β‐defensins showed marked regionalized expression, including the porcine β‐defensins 3 (pBD3), 4 (pBD4), 125 (pBD125) and epididymal protein splicing variant 2C (pEP2C; Guyonnet, Dacheux, Dacheux, & Gatti, ).…”