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    Increased microRNA-155 expression in the serum and peripheral monocytes in chronic HCV infection

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    Authors
    Bala, Shashi
    Tilahun, Yaphet
    Taha, Odette
    Alao, Hawau
    Kodys, Karen
    Catalano, Donna
    Szabo, Gyongyi
    Student Authors
    Odette Taha
    UMass Chan Affiliations
    Medicine
    School of Medicine
    Document Type
    Journal Article
    Publication Date
    2012-07-30
    Keywords
    Hepatitis C, Chronic
    MicroRNAs
    Digestive System Diseases
    Virus Diseases
    
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    Link to Full Text
    https://doi.org/10.1186/1479-5876-10-151
    Abstract
    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-naive (cHCV) but not treatment responder patients showed increased expression of miR-155, a positive regulator of TNFalpha, and had increased TNFalpha 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 TNFalpha 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 TNFalpha 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.
    Source

    Bala S, Tilahun Y, Taha O, Alao H, Kodys K, Catalano D, Szabo G. Increased microRNA-155 expression in the serum and peripheral monocytes in chronic HCV infection. J Transl Med. 2012 Jul 30;10:151. doi: 10.1186/1479-5876-10-151. PMID: 22846613; PMCID: PMC3477071.

    DOI
    10.1186/1479-5876-10-151
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/31051
    PubMed ID
    22846613
    Rights

    © 2012 Bala et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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    10.1186/1479-5876-10-151
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