Arginine alleviates α toxin-induced intestinal injury and via the SLC38A9/mTORC1 pathway.

INTRODUCTION

α toxin is a main virulence factor responsible for gut damage in animals. Arginine is a functional amino acid exhibiting significant immunoregulatory activities. However, the effects and immunoregulatory mechanisms of arginine supplementation on α toxin-induced intestinal injury remain unclear.

METHODS

, 256 male Arbor Acres chickens were randomly assigned to a 2×2 factorial arrangement, involving diet treatments (with or without 0.3% arginine supplementation) and immunological stress (with or without α toxin challenge). , IEC-6 cells were treated with or without arginine in the presence or absence of α toxin. Moreover, IEC-6 cells were transfected with siRNA targeting mTOR and SLC38A9 to explore the underlying mechanisms.

RESULTS AND DISCUSSION

The results showed that , arginine supplementation significantly alleviated the α toxin-induced growth performance impairment, decreases in serum immunoglobulin (Ig)A and IgG levels, and intestinal morphology damage. Arginine supplementation also significantly reduced the α toxin-induced increase in jejunal proinflammatory cytokines interleukin , and mRNA expression. α toxin significantly decreased jejunal mechanistic target of rapamycin and solute carrier family 38 member 9 ( mRNA expression, while arginine supplementation significantly increased and mRNA expression. , arginine pretreatment mitigated the α toxin-induced decrease in cell viability and the increase in cytotoxicity and apoptosis. Arginine pretreatment also alleviated the α toxin-induced upregulation of mRNA expression of inflammation-related cytokines , C-X-C motif chemokine ligand (), and transforming growth factor-β (), as well as apoptosis-related genes B-cell lymphoma-2 associated X protein (), B-cell lymphoma-2 (), B-cell lymphoma-extra large () and cysteinyl aspartate specific proteinase 3 () and the ratio of to . Arginine pretreatment significantly increased the α toxin-induced decrease in , , eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 () and ribosomal protein S6 kinase () mRNA expression. Knockdown SLC38A9 and mTOR largely abrogated the positive effects of arginine pretreatment on α toxin-induced intracellular changes. Furthermore, SLC38A9 silencing abolished the increased mRNA expression caused by arginine pretreatment. In conclusion, arginine administration attenuated α toxin-induced intestinal injury and , which could be associated with the downregulation of inflammation via regulating SLC38A9/mTORC1 pathway.