<scp>l</scp>-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
Jing Lan, Xiujing Dou, Jiawei Li, Yang Yang, Chenyu Xue, Chenxi Wang, Nan Gao, Anshan Shan
Abstract
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-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 (p < 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.