Dopamine Inhibits the Expression of Hepatitis B Virus Surface and e Antigens by Activating the JAK/STAT Pathway and Upregulating Interferon-stimulated Gene 15 Expression  

作　　者：Xiaoquan Liu Xiuqing Pang Zhiping Wan Jinhua Zhao Zhiliang Gao Hong Deng 

机构地区：[1]Department of Infectious Diseases,Third Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong,China [2]Guangdong Key Laboratory of Liver Disease Research,Third Affiliated Hospital of Sun Yat-sen University,Guangzhou Guangdong,China [3]Key Laboratory of Tropical Disease Control(Sun Yat-sen University),Ministry of Education,Guangzhou,Guangdong,China

出　　处：《Journal of Clinical and Translational Hepatology》2024年第5期443-456,共14页临床与转化肝病杂志（英文版）

基　　金：supported by a grant from the National Natural Science Foundation of China(82170612);Guangzhou Science and Technology Program Key Projects(2023B01J1007);National Natural Science Foundation of China(No.81870597).

摘　　要：Background and Aims:Hepatitis B virus(HBV)infection is a major risk factor for cirrhosis and liver cancer,and its treatment continues to be difficult.We previously demonstrated that a dopamine analog inhibited the packaging of pregenomic RNA into capsids.The present study aimed to determine the effect of dopamine on the expressions of hepatitis B virus surface and e antigens(HBsAg and HBeAg,respectively)and to elucidate the underlying mechanism.Methods:We used dopamine-treated HBVinfected HepG2.2.15 and NTCP-G2 cells to monitor HBsAg and HBeAg expression levels.We analyzed interferon-stimulated gene 15(ISG15)expression in dopamine-treated cells.We knocked down ISG15 and then monitored HBsAg and HBeAg expression levels.We analyzed the expression of Janus kinase(JAK)/signal transducer and activator of transcription(STAT)pathway factors in dopamine-treated cells.We used dopamine hydrochloride-treated adeno-associated virus/HBV-infected mouse model to evaluate HBV DNA,HBsAg,and HBeAg expression.HBV virus was collected from HepAD38.7 cell culture medium.Results:Dopamine inhibited HBsAg and HBeAg expression and upregulated ISG15 expression in HepG2.2.15 and HepG2-NTCP cell lines.ISG15 knockdown increased HBsAg and HBeAg expression in HepG2.2.15 cells.Dopamine-treated cells activated the JAK/STAT pathway,which upregulated ISG15 expression.In the adeno-associated virus-HBV murine infection model,dopamine downregulated HBsAg and HBeAg expression and activated the JAK-STAT/ISG15 axis.Conclusions:Dopamine inhibits the expression of HBsAg and HBeAg by activating the JAK/STAT pathway and upregulating ISG15 expression.

关 键 词：Hepatitis B virus DOPAMINE JAK-STAT/ISG15 axis HBV surface antigen HBV e antigen HepG2.2.15 cell line Human NTCP-expressing HepG2 cell line HepAD38 cell line 

分 类 号：R512.62[医药卫生—内科学]