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The impact of chronic hepatitis C infection on cholesterol metabolism in PBMCs is associated with microRNA-146a expression

  • M. SidorkiewiczEmail author
  • M. Grek
  • B. Jozwiak
  • A. Krol
  • A. Piekarska
Original Article

Abstract

Chronic hepatitis C (CHC) infection is known to induce important changes in host cholesterol metabolism. MicroRNAs (miRNAs) regulate the expression of many genes and, in consequence, control various processes, including human metabolism and response to viral infection. Recently, the alteration of the immune-associated miR-146a, which is abundantly present in peripheral blood mononuclear cells (PBMCs), was found in some viral infections. The study aimed to analyse the influence of hepatitis C virus (HCV) infection on miR-146a expression in PBMCs in vivo and in vitro, as well as to assess the possible impact of miR-146a alteration on the intracellular cholesterol level in PBMCs. Blood samples collected from 42 healthy donors and 72 CHC patients were the source of materials. HCV RNA, intracellular cholesterol level and miR-146a expression were determined in PBMCs, as well as HCV genotype and interferon (IFN)α concentration in sera. The influence of miR-146a inhibition on cholesterol expression in PBMCs was analysed in vitro after transient cell transfections with mirVana™ anti-miR-146a Inhibitor. Our data demonstrated an alteration of miR-146a and intracellular cholesterol expression in PBMCs and of IFNα concentration in sera of genotype 1, HCV-infected patients compared to the healthy donors. Also, in cultured PBMCs, miR-146a expression and intracellular cholesterol level were significantly decreased in CHC patients compared to the healthy donors. In vitro blockage of miR-146a expression in PBMCs of CHC patients greatly impaired intracellular cholesterol expression. In these conditions, miR-146a expression was positively correlated with the intracellular cholesterol level. These results suggest that genotype 1 HCV infection may alter miR-146a expression in PBMCs and, consequently, contribute to the observed dysregulation of cholesterol synthesis.

Keywords

Healthy Donor Intracellular Cholesterol Geranylgeranyl Pyrophosphate Intracellular Cholesterol Level PBMCs Sample 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Compliance with ethical standards

Funding

This study was conducted with the financial support of the Ministry of Science and Higher Education of Poland (no. N401098536) and the statutory funds of the Medical University of Lodz (503-6-086-01).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study were in accordance with the ethical standards of the Resolution (RNN/93/07/KB) of the Bioethical Committee of the Medical University of Lodz and with the 1964 Helsinki Declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • M. Sidorkiewicz
    • 1
    Email author
  • M. Grek
    • 1
  • B. Jozwiak
    • 1
  • A. Krol
    • 1
  • A. Piekarska
    • 2
  1. 1.Department of Medical BiochemistryMedical University of LodzLodzPoland
  2. 2.Department of Infectious Diseases and HepatologyMedical University of LodzLodzPoland

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