L-Arginine Inhibited Inflammatory Response and Oxidative Stress Induced by Lipopolysaccharide via Arginase-1 Signaling in IPEC-J2 Cells

Abstract

This study aimed to explore the effect of L-arginine on lipopolysaccharide (LPS)-induced inflammatory response and oxidative stress in IPEC-2 cells. We found that the expression of toll-like receptor 4 (<i>TLR4</i>), myeloid differentiation primary response 88 (<i>MyD88</i>), cluster of differentiation 14 <i>(CD14)</i>, nuclear factor-kappaBp65 (<i>NF-κBp65</i>), chemokine-8 (<i>IL-8</i>), tumor necrosis factor (<i>TNF-α)</i> and chemokine-6 (<i>IL-6</i>) mRNA were significantly increased by LPS. Exposure to LPS induced oxidative stress as reactive oxygen species (ROS) and malonaldehyde (MDA) production were increased while glutathione peroxidase (GSH-Px) were decreased in LPS-treated cells compared to those in the control. LPS administration also effectively induced cell growth inhibition through induction of G0/G1 cell cycle arrest. However, compared with the LPS group, cells co-treatment with L-arginine effectively increased cell viability and promoted the cell cycle into the S phase; L-arginine exhibited an anti-inflammatory effect in alleviating inflammation induced by LPS by reducing the abundance of <i>TLR4</i>, <i>MyD88</i>, <i>CD14</i>, <i>NF-κBp65</i>, and <i>IL-8</i> transcripts. Cells treated with LPS+L-arginine significantly enhanced the content of GSH-Px, while they decreased the production of ROS and MDA compared with the LPS group. Furthermore, L-arginine increased the activity of arginase-1 (Arg-1), while Arg-1 inhibitor abolished the protection of arginine against LPS-induced inflammation and oxidative stress. Taken together, these results suggested that L-arginine exerted its anti-inflammatory and antioxidant effects to protect IPEC-J2 cells from inflammatory response and oxidative stress challenged by LPS at least partly via the Arg-1 signaling pathway.