GPR43 regulates HBV X protein (HBx)-induced inflammatory response in human LO2 hepatocytes.

Abstract

The present study investigated the role of G coupled-protein receptor 43 (GPR43), also known as free fatty acid receptor 2 (FFAR2), in regulating the cytotoxic effects of hepatitis B virus (HBV) by transfecting hepatitis B protein X (HBx) into human LO2 hepatocytes. To our knowledge, this study is the first to demonstrate the role of GPR43 in LO2 hepatocytes and to show that transfection with HBx suppresses GPR43 expression. HBx contributes to inflammation by triggering the release of proinflammatory cytokines including interleukin-6 (IL-6), monocyte chemoattractant protein (MCP-1), (C-X-C motif) ligand 2 (CXCL2), and high mobility group box 1 protein (HMGB1). Additionally, HBx induces oxidative stress by upregulating the production of ROS. We performed a series of experiments using the human LO2 cell line and the specific GPR43 agonist (S)-2-(4-chlorophenyl)-3,3-dimethyl-N-(5-phenyl thiazole-2-yl) butanamide (PA). We found that agonism of GPR43 significantly ameliorated HBx-induced expression of proinflammatory cytokines and chemokines, and lowered the level of oxidative stress. Notably, we demonstrate that these effects of PA are mediated through inhitibing the phosphorylation of p38 and activation of the IκBα/nuclear factor-κB (NF-κB) pathway. Together, our findings provide compelling evidence of the potential for GPR43 as a treatment target against HBx-induced inflammatory response.

• Authors: Tao He, Ning Zhang, Li Wang, Baishun Wan, Xiaoqian Wang, Ling Zhang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 123 Pg. 109737 (Mar 2020) ISSN: 1950-6007 [Electronic] France
• PMID: 31884344 (Publication Type: Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier Masson SAS.

Chemical References

• Cytokines
• FFA2R protein, human
• Receptors, Cell Surface
• Trans-Activators
• Viral Regulatory and Accessory Proteins
• hepatitis B virus X protein

Topics

• Cell Line
• Cytokines (genetics, metabolism)
• Gene Expression Regulation (drug effects, physiology)
• Hepatocytes (drug effects, metabolism)
• Humans
• Oxidative Stress
• Receptors, Cell Surface (agonists, genetics, metabolism)
• Trans-Activators (toxicity)
• Transfection
• Viral Regulatory and Accessory Proteins (toxicity)