l-Arginine Ameliorates Lipopolysaccharide-Induced Intestinal Inflammation through Inhibiting the TLR4/NF-κB and MAPK Pathways and Stimulating β-Defensin Expression in Vivo and in Vitro.

Nutritional regulation of endogenous antimicrobial peptide (AMP) expression is considered a promising nonantibiotic approach to suppressing intestinal infection of pathogen. The current study investigated the effects of l-arginine on LPS-induced intestinal inflammation and barrier dysfunction in vivo and in vitro. The results revealed that l-arginine attenuated LPS-induced inflammatory response, inhibited the downregulation of tight junction proteins (TJP) ( < 0.05) by LPS, and maintained intestinal integrity. In porcine intestinal epithelial cells (IPEC-J2), l-arginine obviously suppressed ( < 0.05) the levels of IL-6 (220.63 ± 2.82), IL-8 (333.95 ± 3.75), IL-1β (693.08 ± 2.38), and TNF-α (258.04 ± 4.14) induced by LPS. Furthermore, l-arginine diminished the LPS-induced expression of Toll-like receptor 4 (TLR4) and inhibited activation of TLR4-mediated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Importantly, we proposed a new mechanism that l-arginine had the ability to stimulate the expression of porcine epithelial β-defensins through activating the mammalian target of the rapamycin (mTOR) pathway, which exerts anti-inflammatory influence. Moreover, pBD-1 gene overexpression decreased ( < 0.05) the TNF-α level stimulated by LPS in IPEC-J2 cells (4.22 ± 1.64). The present study indicated that l-arginine enhanced disease resistance through inhibiting the TLR4/NF-κB and MAPK pathways and partially, possibly through increasing the intestinal β-defensin expression.