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Involvement of the Interleukin-23/Interleukin-17 Axis in Chronic Hepatitis C Virus Infection and Its Treatment Responses.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2016 Jul 15; Vol. 17 (7). Date of Electronic Publication: 2016 Jul 15. - Publication Year :
- 2016
-
Abstract
- Interleukin-23 (IL-23) and its downstream factor IL-17 are the key cytokines involved in immune and inflammatory response in chronic liver diseases. This study aimed to investigate the role and molecular mechanisms of the IL-23/Th17 axis in chronic hepatitis C virus (HCV) infection, and the efficacy of IL-23/Th17 modulation in response to anti-HCV therapy. Sixty-six HCV-infected patients and 20 healthy controls were enrolled. The patients received PegIFNa-2a and ribavirin therapy for at least 48 weeks. The plasma level of IL-23 and the number of IL-17A-, IFN-γ-, and IL-21-producing peripheral blood mononuclear cells (PBMCs) at baseline and 12, 24, and 48 weeks following treatment were determined. The mRNA level of Th17 immune-associated molecules in PBMCs was evaluated by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) following treatment with IL-23 agonist or antagonist. Our data showed that, compared to healthy controls, HCV-infected patients had an increased plasma level of IL-23 and increased frequencies of IL-17A- and IFN-γ-producing PBMCs, whereas the HCV patients exhibited a reduced number of IL-21-producing PBMCs. However, the baseline frequencies of IL-21-producing PBMCs were markedly higher in HCV patients who achieved rapid virological response (RVR) than those without RVR. Additionally, the mRNA expressions of IL-21, IFN-γ, myxovirus resistance protein A (MxA), and suppressor of cytokine signaling 3 (SOCS3) were significantly upregulated in PBMCs, while FoxP3 expression was suppressed by IL-23 agonist. Thus, the IL-23/Th17 axis plays an important role in development of chronic HCV infection and antiviral response. IL-23 may enhance the antiviral activity of interferon-based therapy by modulating the expression of Th17 cells-associated molecules in HCV-infected patients.
- Subjects :
- Adolescent
Adult
Aged
Enzyme-Linked Immunosorbent Assay
Female
Flow Cytometry
Hepacivirus physiology
Hepatitis C, Chronic metabolism
Hepatitis C, Chronic pathology
Humans
Interleukin-17 genetics
Interleukin-23 genetics
Male
Middle Aged
Real-Time Polymerase Chain Reaction
Recombinant Proteins pharmacology
Young Adult
Antiviral Agents pharmacology
Hepatitis C, Chronic drug therapy
Interferon-alpha pharmacology
Interleukin-17 metabolism
Interleukin-23 metabolism
Polyethylene Glycols pharmacology
Ribavirin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 17
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 27428948
- Full Text :
- https://doi.org/10.3390/ijms17071070