L-Arginine Ameliorates Lipopolysaccharide-Induced Intestinal Inflammation through Inhibiting the TLR4/NF-kappa B and MAPK Pathways and Stimulating beta-Defensin Expression in Vivo and in Vitro

摘要

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) (p < 0.05) by LPS, and maintained intestinal integrity. In porcine intestinal epithelial cells (IPEC-J2), L-arginine obviously suppressed (p < 0.05) the levels of IL-6 (220.63 +/- 2.82), IL-8 (333.95 +/- 3.75), IL-1 beta (693.08 +/- 2.38), and TNF-alpha (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-kappa B) 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 beta-defensins through activating the mammalian target of the rapamycin (mTOR) pathway, which exerts anti-inflammatory influence. Moreover, pBD-1 gene overexpression decreased (p < 0.05) the TNF-alpha 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-kappa B and MAPK pathways and partially, possibly through increasing the intestinal beta-defensin expression.