首页|血红素加氧酶-1通过诱导抗病毒蛋白的表达增强IFN-α抗HBV效应

血红素加氧酶-1通过诱导抗病毒蛋白的表达增强IFN-α抗HBV效应

Heme oxygenase-1 enhances the anti-HBV effect of IFN-αby inducing the expression of antiviral proteins

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目的 探讨血红素加氧酶-1(HO-1)对HBV复制的作用及HO-1联合α-干扰素(IFN-α)的抗病毒效应.方法 以HepG2.2.15细胞和HBV 1.3质粒转染HepG2细胞即HepG2-HBV1.3为HBV复制细胞模型;血红素(Hemin)分别处理 HepG2.2.15 和 HepG2-HBV1.3 细胞,诱导 HO-1 表达;CCK-8评估Hemin对HepG2、HepG2.2.15的毒性作用;化学发光法分析Hemin处理组及si-HO-1等实验组上清液中HB-sAg、HBeAg;RT-qPCR 分析 HO-1、IFN-β、HBV-DNA;Western blot分析IRF-3、JAK/STAT信号通路中相关分子的表达;He-min 联合IFN-α处理HepG2.2.15,监测HO-1是否具有协同IFN-α抗病毒效应.结果 Hemin剂量依赖性诱导HO-1,HO-1被诱导后发挥显著的抗HBV效应,同时IFN-β、IRF-3及JAK/STAT信号通路中IRF-9、MxA的表达均增加.沉默HO-1表达能逆转Hemin诱导组的抗病毒效应,同时I型干扰素IFN-β也呈现低表达,JAK/STAT信号通路中的IRF-9、MxA的表达也被抑制.Hemin联合IFN-α发挥更强的抗病毒作用.结论 HO-1能够发挥抗HBV效应,这种效应可能是增加IRF-3的磷酸化诱导Ⅰ型干扰素表达来激活JAK/STAT信号通路发挥抗病毒效应;HO-1可以协同IFN-α发挥抗病毒作用.
Objective To investigate the role of heme oxygenase-1(HO-1)on HBV replication and the antiviral effect of HO-1 combined with α-interferon(IFN-α).Methods HepG2.2.15 cells and HBV1.3-transfected HepG2 cells(HepG2-HBV1.3)were used as HBV replicating cell models;Hemin treated HepG2.2.15 and HepG2-HBV1.3 cells,to induce the expression of HO-1 molecules.CCK-8 method was used to assess the toxic effects of Hemin on HepG2 and HepG2.2.15;chemiluminescence method was used to analyze HBsAg and HBeAg in the supernatants of Hemin-treated group and si-HO-1 and other experimental groups;RT-qPCR was used to ana-lyze HO-1,IFN-β and HBV-DNA;Western blot was used to analyze the expression of IRF-3 and the expression of related molecules in the JAK/STAT signaling pathway;Hemin combined with IFN-α treated HepG2.2.15 to moni-tor whether HO-1 had synergistic IFN-α antiviral effect.Results Hemin dose-dependently induced HO-1,and HO-1 was induced to exert a significant anti-HBV effect,while the expression of IFN-β,IRF-3,and IRF-9 and MxA,downstream molecules of the JAK/STAT signaling pathway,were all increased.Silencing HO-1 expression reversed the antiviral effect in the Hemin-induced group,and at the same time,type Ⅰ interferon IFN-β showed low expression,and the expression of IRF-9 and MxA in the JAK/STAT signaling pathway was inhibited as well.He-min combined with IFN-α exerted stronger antiviral effects.Conclusion HO-1 can exert an anti-HBV effect,which may be due to increased phosphorylation of IRF-3 to induce type Ⅰ interferon expression and thus activate the JAK/STAT signaling pathway to exert an antiviral effect;HO-1 can synergize with IFN-α to exert an antiviral effect.

heminheme oxygenase-1JAK/STATIFN-β

笪蔚、王琴、魏安邦、张浩、汪任冰、刘倩、周强

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安徽医科大学第二附属医院检验科,合肥 230601

安徽医科大学第二附属医院儿科,合肥 230601

血红素 血红素加氧酶-1 JAK/STAT IFN-β

安徽省转化医学研究院科研项目安徽省高等学校自然科学研究重点项目

2021zhyx-C472023AH053169

2024

安徽医科大学学报
安徽医科大学

安徽医科大学学报

CSTPCD北大核心
影响因子:1.095
ISSN:1000-1492
年,卷(期):2024.59(2)
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