Zhang Hao, Guan Zi-Shu, Guan Shi-He, Yang Kai, Pan Ying, Wu Yuan-Yuan, Wang Ai-Hua, Sun Bei-Bei, Hou Jie, Mu Xuan-Xuan, Gao Yu-Feng, Cheng Wei-Sheng
Clin Lab. 2016 Dec 1;62(12):2313-2318. doi: 10.7754/Clin.Lab.2016.160318.
The primary aim of this study is to measure the JAK-STAT signaling in HBV infected peripheral blood mononuclear cells (PBMCs) stimulated by IFN-α and 3-TC and explore the influence of HBV to the JAKSTAT signaling pathways.
PBMCs were separated from healthy volunteers and patients who had not received any treatment with chronic hepatitis B. PBMCs were divided into the control group, IFN-α stimulation group, Lamivudine stimulation group, and combined treatment group. The expression of molecules of JAK-STAT signal transduction pathway (STAT1, STAT2, IRF9) and the antiviral protein (MxA) were detected by RT-qPCR and Western blot method.
The majority of IFN-α inducible genes were expressed. The molecules of JAK-STAT signal transduction pathway (STAT1, STAT2, IRF9) and the antiviral protein (MxA) were highly expressed in IFN-α stimulation group and the combined treatment group. Compared to healthy controls, the expression levels of molecules (STAT1, IRF9) and the antiviral protein (MxA) are significantly lower in the control group, IFN-α stimulation group, and the combined treatment group of the CHB patients.
IFN-α could activate JAK-STAT signaling transduction pathway in PBMCs of HBV-infected patients and HBV might process the activity to antagonize the antiviral activity in HBV infected PBMCs.
本研究的主要目的是检测经干扰素-α(IFN-α)和拉米夫定(3-TC)刺激的乙肝病毒(HBV)感染的外周血单个核细胞(PBMCs)中的JAK-STAT信号传导,并探讨HBV对JAK-STAT信号通路的影响。
从健康志愿者和未接受过任何治疗的慢性乙型肝炎患者中分离PBMCs。将PBMCs分为对照组、IFN-α刺激组、拉米夫定刺激组和联合治疗组。采用逆转录定量聚合酶链反应(RT-qPCR)和蛋白质免疫印迹法检测JAK-STAT信号转导通路分子(STAT1、STAT2、IRF9)和抗病毒蛋白(MxA)的表达。
大多数IFN-α诱导基因得以表达。JAK-STAT信号转导通路分子(STAT1、STAT2、IRF9)和抗病毒蛋白(MxA)在IFN-α刺激组和联合治疗组中高表达。与健康对照组相比,慢性乙型肝炎患者的对照组、IFN-α刺激组和联合治疗组中分子(STAT1、IRF9)和抗病毒蛋白(MxA)的表达水平显著降低。
IFN-α可激活HBV感染患者PBMCs中的JAK-STAT信号转导通路,且HBV可能具有拮抗HBV感染的PBMCs中抗病毒活性的作用。