慢性 HCV 感染患者血清和外周血单核细胞中 microRNA-155 表达增加。
Increased microRNA-155 expression in the serum and peripheral monocytes in chronic HCV infection.
机构信息
Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
出版信息
J Transl Med. 2012 Jul 30;10:151. doi: 10.1186/1479-5876-10-151.
BACKGROUND
Hepatitis C Virus (HCV), a single stranded RNA virus, affects millions of people worldwide and leads to chronic infection characterized by chronic inflammation in the liver and in peripheral immune cells. Chronic liver inflammation leads to progressive liver damage. MicroRNAs (miRNA) regulate inflammation (miR-155, -146a and -125b) as well as hepatocyte function (miR-122).
METHODS
Here we hypothesized that microRNAs are dysregulated in chronic HCV infection. We examined miRNAs in the circulation and in peripheral monocytes of patients with chronic HCV infection to evaluate if specific miRNA expression correlated with HCV infection.
RESULTS
We found that monocytes from chronic HCV infected treatment-naïve (cHCV) but not treatment responder patients showed increased expression of miR-155, a positive regulator of TNFα, and had increased TNFα production compared to monocytes of normal controls. After LPS stimulation, miR-155 levels were higher in monocytes from cHCV patients compared to controls. MiR-125b, which has negative regulatory effects on inflammation, was decreased in cHCV monocytes compared to controls. Stimulation of normal monocytes with TLR4 and TLR8 ligands or HCV core, NS3 and NS5 recombinant proteins induced a robust increase in both miR-155 expression and TNFα production identifying potential mechanisms for in vivo induction of miR-155. Furthermore, we found increased serum miR-155 levels in HCV patients compared to controls. Serum miR-125b and miR-146a levels were also increased in HCV patients. Serum levels of miR-122 were elevated in cHCV patients and correlated with increased ALT and AST levels and serum miR-155 levels.
CONCLUSION
In conclusion, our novel data demonstrate that miR-155, a positive regulator of inflammation, is upregulated both in monocytes and in the serum of patients with chronic HCV infection. Our study suggests that HCV core, NS3, and NS5 proteins or TLR4 and TLR8 ligands can mediate increased miR-155 and TNFα production in chronic HCV infection. The positive correlation between serum miR-155 and miR-122 increase in cHCV may be an indicator of inflammation-induced hepatocyte damage.
背景
丙型肝炎病毒（HCV）是一种单链 RNA 病毒，影响着全球数百万人，导致慢性感染，其特征是肝脏和外周免疫细胞的慢性炎症。慢性肝炎症导致进行性肝损伤。微小 RNA（miRNA）调节炎症（miR-155、-146a 和 -125b）和肝细胞功能（miR-122）。
方法
在这里，我们假设微小 RNA 在慢性 HCV 感染中失调。我们检测了慢性 HCV 感染患者的循环和外周单核细胞中的 miRNA，以评估特定 miRNA 表达是否与 HCV 感染相关。
结果
我们发现，来自慢性 HCV 感染未经治疗（cHCV）但未治疗应答患者的单核细胞显示出 miR-155 的表达增加，miR-155 是 TNFα 的正调节剂，并且与正常对照单核细胞相比，TNFα 的产生增加。在用 LPS 刺激后，cHCV 患者的单核细胞中的 miR-155 水平高于对照。miR-125b 对炎症具有负调节作用，与对照相比，cHCV 单核细胞中的 miR-125b 减少。用 TLR4 和 TLR8 配体或 HCV 核心、NS3 和 NS5 重组蛋白刺激正常单核细胞可诱导 miR-155 表达和 TNFα 产生的强烈增加，从而确定体内诱导 miR-155 的潜在机制。此外，我们发现与对照相比，HCV 患者的血清 miR-155 水平升高。HCV 患者的血清 miR-125b 和 miR-146a 水平也升高。cHCV 患者的血清 miR-122 水平升高，与 ALT 和 AST 水平以及血清 miR-155 水平升高相关。
结论
总之，我们的新数据表明，炎症的正调节剂 miR-155 在慢性 HCV 感染的单核细胞和血清中均上调。我们的研究表明，HCV 核心、NS3 和 NS5 蛋白或 TLR4 和 TLR8 配体可介导慢性 HCV 感染中 miR-155 和 TNFα 产生的增加。cHCV 中血清 miR-155 和 miR-122 增加的正相关可能是炎症诱导的肝细胞损伤的指标。
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