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慢性丙型肝炎感染患者外周血单个核细胞中Toll样受体3和7的独特表达

Distinct Toll-like Receptor 3 and 7 Expression in Peripheral Blood Mononuclear Cells From Patients with Chronic Hepatitis C Infection.

作者信息

Motavaf Mahsa, Noorbakhsh Fatemeh, Alavian Seyed Moayed, Sharifi Zohreh

机构信息

Department of Microbiology, Islamic Azad University of Varamin-Pishva, Varamin, IR Iran ; Department of Molecular Hepatology, Middle East Liver Disease Center (MELD), Tehran, IR Iran.

Department of Microbiology, Islamic Azad University of Varamin-Pishva, Varamin, IR Iran.

出版信息

Hepat Mon. 2014 Apr 7;14(4):e16421. doi: 10.5812/hepatmon.16421. eCollection 2014 Apr.

Abstract

BACKGROUND

Hepatitis C virus (HCV) is a major cause of chronic liver disease, with around 130 million infected people worldwide. HCV is recognized by Toll-like receptors (TLRs), which are key mediators of innate immune response. Up on activation of TLRs, anti-viral cytokines and pre-inflammatory are produced.

OBJECTIVES

In this study, we compared the expression levels of two members of the TLR family (TLR3 and TLR7) that recognize viral RNA in peripheral blood mononuclear cell (PBMC) of patients with chronic HCV infection and healthy controls.

PATIENTS AND METHODS

In this case-control study, blood samples were collected from patients admitted to Blood Transfusion Research Center, Tehran, Iran. PBMC was isolated from blood of chronic HCV patients (n = 25) and age and sex-matched healthy controls (n = 25). RNA was extracted from PBMC and cDNA was synthesized from total RNA templates using reverse transcriptase. The relative level of expression was quantified by real-time PCR using Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as reference gene and the results were compared by Pfaffl method. Data were analyzed using non-parametric Wilcoxon test. P < 0.05 was considered significant.

RESULTS

In both groups, we had 13 males and 12 females with a mean age of 48.7 ± 16. TLR3 (6.23 ± 0.91 vs. 3.89 ± 0.85, P < 0.001) and TLR7 (1.48 ± 0.82 vs-1.33 ± 1.18, P < 0.001) expressions were significantly lower in patients with chronic HCV infection when compared with healthy controls.

CONCLUSIONS

This study suggests that decrease in levels of TLR3 and TLR7 expression is a mechanism that may enable HCV to evade the host innate immune response.

摘要

背景

丙型肝炎病毒(HCV)是慢性肝病的主要病因,全球约有1.3亿感染者。HCV可被Toll样受体(TLR)识别,TLR是先天免疫反应的关键介质。TLR激活后,会产生抗病毒细胞因子和促炎因子。

目的

在本研究中,我们比较了识别病毒RNA的TLR家族两个成员(TLR3和TLR7)在慢性HCV感染患者和健康对照者外周血单核细胞(PBMC)中的表达水平。

患者与方法

在这项病例对照研究中,从伊朗德黑兰输血研究中心收治的患者中采集血样。从慢性HCV患者(n = 25)以及年龄和性别匹配的健康对照者(n = 25)的血液中分离出PBMC。从PBMC中提取RNA,并使用逆转录酶从总RNA模板合成cDNA。以甘油醛-3-磷酸脱氢酶(GAPDH)作为参考基因,通过实时PCR对相对表达水平进行定量,并采用Pfaffl法比较结果。使用非参数Wilcoxon检验分析数据。P < 0.05被认为具有统计学意义。

结果

两组中均有13名男性和12名女性,平均年龄为48.7±16岁。与健康对照者相比,慢性HCV感染患者的TLR3(6.23±0.91对3.89±0.85,P < 0.001)和TLR7(1.48±0.82对1.33±1.18,P < 0.001)表达显著降低。

结论

本研究表明,TLR3和TLR7表达水平降低可能是HCV逃避宿主先天免疫反应的一种机制。

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