Inhibition of Protease Activated Receptor 2 Attenuates HBx-Induced Inflammation and Mitochondria Oxidative Stress

BACKGROUND: 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 LO(2) 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 LO(2) 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-NH(2) (PAR2 antagonist) treated LO(2) 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.