The Synergistic Effect of Fluvastatin and IFN-λ on Peripheral Blood Mononuclear Cells of Chronic Hepatitis C Virus (HCV) Patients with IL-28B rs12979860 CC Genotype

Synergistic effect of Fluvastatin and Lambda interferon

  • Amin Farzanegan Gharabolagh Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  • Taravat Bamdad Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  • Mehdi Hedayati Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Seyed Ali Dehghan Manshadi Department of Infectious Diseases and Tropical Medicine, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
Keywords: ATP-binding cassette transporter A1 (ABCA1), Diacylglycerol acyltransferase 1 (DGAT1), Fluvastatin, Hepatitis C virus, Interferon lambda, IL-28B, Sterol regulatory element-binding protein 1c (SREBP1c)

Abstract

There is a relationship between the life cycle of the hepatitis C virus (HCV) and the synthesis and hemostasis of lipids as well as lipid metabolism and interferon (IFN) regulatory system. This study was aimed to examine the effect of fluvastatin and IFN-ƛ in the expression of mediators involved in lipid metabolism and HCV proliferation in patients with rs12979860 CC polymorphism. Thirteen patients with HCV and five controls with rs1297986CC polymorphism were included in this study. Peripheral blood mononuclear cells (PBMCs) of patients and controls were treated by fluvastatin, IFN-λ or fluvastatin+IFN-λ. Assessment of IL-28B polymorphism, RNA extraction, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed. The mRNA expression of sterol regulatory element-binding protein 1 c (SREBP1c), ATP-binding cassette transporter A1 (ABCA1), diacylglycerol acyltransferase 1 (DGAT1), and HCV core as well as measurement of ABCA1 protein level were evaluated before and after treatment. The results indicated that IFN-λ +fluvastatin acted as an inhibitor in mRNA expression of SREBP1c; while acting as an inducer in the expression of ABCA-1. The results of ABCA1 assay showed a significant increase of this protein after treatment with fluvastatin and IFN-λ compared with untreated cells (p=0.02). Moreover, the mRNA expression of HCV core was suppressed in all experimental groups treated with fluvastatin, IFN-λ or their combination which was more significant after treatment with fluvastatin+IFN-λ (p<0.001). The results of this study demonstrated the significant effect of treatment with fluvastatin+IFN-λ in PBMCs of HCV patients with rs12979860 CC polymorphism. According to the drug resistance of viruses and prevention of virus-induced steatosis in patients with HCV, using regulatory agents of lipid mediators in parallel with current medications could be considered as an effective therapeutic strategy.

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Published
2019-10-23
How to Cite
1.
Farzanegan Gharabolagh A, Bamdad T, Hedayati M, Dehghan Manshadi SA. The Synergistic Effect of Fluvastatin and IFN-λ on Peripheral Blood Mononuclear Cells of Chronic Hepatitis C Virus (HCV) Patients with IL-28B rs12979860 CC Genotype. Iran J Allergy Asthma Immunol. 18(5):533-542.
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Original Article(s)