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The hepatitis C virus core protein indirectly induces alpha-smooth muscle actin expression in hepatic stellate cells via interleukin-8

Pascarella, Stephanie
Conzelmann, Stéphanie
Published in Journal of hepatology. 2010, vol. 52, no. 5, p. 635-643
Abstract BACKGROUND & AIMS: Progressive deposition of liver fibrosis is a common feature of chronic hepatitis associated with hepatitis C virus (HCV) infection, and it may eventually lead to cirrhosis and liver failure. Although this fibrogenic process appears to be linked to HCV protein expression and replication via indirect mechanisms, i.e., to be mediated by virally-driven inflammation, a direct role of HCV in inducing fibrosis deposition has never been entirely excluded. METHODS: We established an in vitro system in which the human hepatic stellate cell line LX-2 was cultured in the presence of conditioned medium from human hepatoma Huh-7 cells transduced with a lentiviral vector expressing HCV core proteins of different genotypes. RESULTS: Treatment of LX-2 cells, with conditioned medium from Huh-7 cells expressing HCV core protein, led to the activation of alpha-smooth muscle actin expression. Among the chemokines secreted by cells transduced with HCV core, interleukin-8 was identified as the strongest inducer of alpha-smooth muscle actin expression in LX-2 and primary hepatic stellate cells. This effect was accompanied by a decrease in cell migration and increased focal contact organisation. CONCLUSIONS: The expression of the HCV core in hepatocytes may contribute to the establishment of a profibrogenic microenvironment.
Keywords Carcinoma, Hepatocellular/epidemiology/pathology/virologyCell MovementCloning, MolecularDNA PrimersDNA, Complementary/geneticsDeveloping CountriesHepacivirus/genetics/*physiologyHepatitis C/complications/epidemiology/*physiopathologyHumansIncidenceInterleukin-8/geneticsLiver Neoplasms/epidemiology/pathology/*virologyPhenylurea CompoundsPolymerase Chain ReactionRNA, Messenger/geneticsRNA, Viral/genetics/isolation & purificationReceptors, Interleukin-8A/geneticsReceptors, Interleukin-8B/geneticsTriazolesTumor Cells, CulturedViral Core Proteins/*physiology
PMID: 20347177
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Research groups Cultures cellulaires et transplantations (519)
Etudes et traitement de l'hépatite C et B (554)
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CLEMENT, Sophie et al. The hepatitis C virus core protein indirectly induces alpha-smooth muscle actin expression in hepatic stellate cells via interleukin-8. In: Journal of hepatology, 2010, vol. 52, n° 5, p. 635-643. doi: 10.1016/j.jhep.2009.10.035 https://archive-ouverte.unige.ch/unige:20853

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Deposited on : 2012-05-23

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