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
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.
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.
The expression of the HCV core in hepatocytes may contribute to the establishment
of a profibrogenic microenvironment.
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