干扰素刺激基因表达对Peg-IFN抗乙型肝炎病毒免疫应答的影响

为了揭示干扰素刺激基因(interferon-stimulated gene, ISG)表达的改变对乙型肝炎病毒感染治疗效果的影响,本研究检测了干扰素刺激基因STAT1、MX和SOCS3在慢性乙型肝炎患者的外周血单核细胞(peripheral blood mononuclear cell, PBMC)和肝脏样品中的表达情况。结果显示,采用聚乙二醇干扰素(Peg-IFN)治疗后,Peg-IFN应答者的PBMC和肝组织中的STAT1和MX表达水平显著升高,而非应答者的SOCS3表达显著升高。在应答者的活组织检查中,Peg-IFN治疗24 h后细胞核中磷酸化STAT1的染色比例显著增加,而非应答者在治疗前肝细胞核染色比例较高,治疗后染色比例显著减少。此外,治疗前非应答者的肝SOCS3表达水平显著高于应答者,并且随着IFN的治疗SOCS3表达继续增加。本研究表明,STAT1和MX是Peg-IFN抗病毒免疫应答的正向调节因子,而SOCS3 (JAK/STAT途径的负调节因子)激活干扰素刺激基因的负调控,并抑制Peg-IFN的免疫应答。

Effects of Interferon Stimulated Gene Expression on Peg-IFN Immune Response against Hepatitis B Virus Infection

In order to reveal the effect of changes in IFN-stimulated gene(ISG) expression on the therapeutic efficacy of hepatitis B virus infection, this study examined the expression of STAT1, MX, and SOCS3 of ISG in peripheral blood mononuclear cells(PBMC) and liver samples from patients with chronic hepatitis B. The results showed that after treatment with Peg-IFN, the expression levels of STAT1 and MX in PBMCs and hepatic tissues of Peg-IFN responders were significantly increased, and the expression of SOCS3 in non-responders was significantly increased.In responder biopsies, the proportion of phosphorylated STAT1 staining in the nucleus was significantly increased after24 h of Peg-IFN treatment. Non-responders had a higher percentage of hepatocyte nuclear staining before treatment and the percentage of staining after treatment was significantly reduced. In addition, the level of liver SOCS3 expression in non-responders before treatment was significantly higher than that in responders, and the expression of SOCS3 continued to increase with the treatment of IFN. This study indicated that STAT1 and MX were positive regulators of the Peg-IFN antiviral immune response,whereas SOCS3, a negative regulator of the JAK/STAT pathway,activated the negative regulation of interferon-stimulated genes and suppresses Peg-IFN immune responses.