Infection and Drug Resistance (Mar 2022)
Inhibition of Protease Activated Receptor 2 Attenuates HBx-Induced Inflammation and Mitochondria Oxidative Stress
Abstract
Bin Li,1 Yonggang Li,2 Shuhua Li,1 Hongwei Li,1 Ling Liu,1 Yao Xu3 1Laboratory of Immunology and Pathogenic Biology, Experimental Teaching Center of Basic Medicine, Jinzhou Medical University, Jinzhou City, Liaoning Province, 121001, People’s Republic of China; 2Department of Pathogenic Biology, School of Basic Medicine, Jinzhou Medical University, Jinzhou City, Liaoning Province, 121001, People’s Republic of China; 3School of Pharmacy, Jinzhou Medical University, Jinzhou City, Liaoning Province, 121001, People’s Republic of ChinaCorrespondence: Yao Xu, School of Pharmacy, Jinzhou Medical University, Jinzhou City, Liaoning Province, 121001, People’s Republic of China, Tel +86 15042606492, Email [email protected]: Hepatitis B virus (HBV) infection is one of the global public problems. Among the known infection cases, HBV X protein (HBx) is one of the key inducements of viral replication and host infection. This study was aimed to uncover the role of protease activated receptor 2 (PAR2) on HBx-induced liver injury.Methods: A PAR2-KO mouse model expressing HBx was constructed using hydrodynamics-based in vivo gene transfection method. In addition, pcDNA3.1-HBx was used to over-express HBx in LO2 cells. The effects of HBx overexpression on inflammation and mitochondria oxidative stress were evaluated.Results: We found that PAR2 protein level was increased by HBx overexpression. The enforced HBx inhibited LO2 cells apoptosis. Meanwhile, HBx induced inflammation reactions through promoting the secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and CXCL-2. Overexpressed HBx also resulted in mitochondria oxidative stress by upregulation of ROS level and downregulation of MMP and ATP. However, in FSLLRY-NH2 (PAR2 antagonist) treated LO2 cells or PAR2-KO mice, PAR2 blockade reversed the above adverse effects of HBx on liver cells or tissues.Conclusion: Inhibition of PAR2 may suppress inflammation and mitochondria oxidative stress caused by HBx, pointing out the potential application values of PAR2 antagonist on the treatment of HBV infection in clinic.Keywords: protease activated receptor 2, hepatitis B virus, hepatitis B virus X protein, inflammation, mitochondria oxidative stress
