Z Gastroenterol 2020; 58(01): e62-e63
DOI: 10.1055/s-0039-3402275
Poster Visit Session V Viral Hepatitis and Immunology: Saturday, February 15, 2020, 11:00 am – 11:45 am, Lecture Hall P1
Georg Thieme Verlag KG Stuttgart · New York

The Hepatitis C Virus influences CXC chemokine expression of infected host cells in response to IL-1β

K Rufinatscha
1   University Hospital Duesseldorf, Heinrich- Heine University, Gastroenterology, Hepatology and Infectious diseases, Düsseldorf, Germany
,
S Stindt
1   University Hospital Duesseldorf, Heinrich- Heine University, Gastroenterology, Hepatology and Infectious diseases, Düsseldorf, Germany
,
J Dobner
2   Heinrich- Heine University, Institut für Physikalische Biologie, Düsseldorf, Germany
,
C Ehlting
1   University Hospital Duesseldorf, Heinrich- Heine University, Gastroenterology, Hepatology and Infectious diseases, Düsseldorf, Germany
,
D Häussinger
1   University Hospital Duesseldorf, Heinrich- Heine University, Gastroenterology, Hepatology and Infectious diseases, Düsseldorf, Germany
,
JG Bode
1   University Hospital Duesseldorf, Heinrich- Heine University, Gastroenterology, Hepatology and Infectious diseases, Düsseldorf, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2020 (online)

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Background & aims:

The Hepatitis C Virus (HCV) employs several strategies to circumvent the antiviral immune response of its host. This also involves modulation of the local and systemic inflammatory response of the host. As it is known that serum levels of inflammatory cytokines such as Interleukin 1β (IL-1β) are upregulated in sera of HCV-infected patients, the present study analyses the impact of HCV on chemokine expression and in particular on the expression of CXCR2 ligands of its host cell in response to stimulation with IL-1β.

Methods:

CXCR2 ligands mRNA levels were determined in cells either harbouring the subgenomic replicon of HCV or in cells infected with HCV (HCVcc) by quantitative real time PCR (qRT-PCR). Cells were transfected with small interfering RNAs (siRNAs) and chemokine expression was determined. Activation of the NFκB subunit p65 was analysed by immunoblot. Binding of p65 to CXCL8 promoter region was determined by chromatin immunoprecipitation (ChIP).

Results:

CXCR2 ligand expression was upregulated in both replicon and HCVcc-infected cells. This HCV-mediated enhancement of chemokine expression was further strengthened upon stimulation with IL-1β. Phosphorylation of the NFκB subunit p65 and p65 binding to the respective binding site of the CXCL8 promoter were enhanced in subgenomic replicon cells in response to IL-1β stimulation. Consistently, knockdown of p65 expression resulted in decreased CXCR2 ligand expression in HCV-infected cells with and without IL-1β stimulation. Transforming growth factor β- activated kinase 1 (TAK1) knockdown led to decreased CXCR2 ligand expression at basal levels but did not affect the effects of HCV-infection and/or IL-1β stimulation. In addition, inhibitor studies suggest that regulation of CXCR2 ligand expression by HCV and/or IL-1β is independent from IKK, p38 MAPK and the proteinkinase B (Akt).

Conclusions:

The present study indicates that HCV enhances basal as well IL-1β-inducible expression of CXCR2 ligands and that this involves NFκB/p65-dependent regulation of gene expression, which is independent from TAK1, IKK, p38 MAPK and Akt.