Abstract
Summary. Chronic hepatitis C infection leads to increased hepatocyte apoptosis. Because engulfment of apoptotic bodies (ABs) by hepatic stellate cells (HSC) is profibrogenic, we compared the effects of ABs derived from hepatitis C virus (HCV)-negative vs HCV-infected (Con1+) Huh7 hepatoblastoma cells on fibrogenic and activation-related mRNA expression by a human HSC line (LX2). Uptake of Huh7 Con1+ ABs by LX2 cells dose dependently upregulated profibrotic genes (COL1A1, TGFB1; TIMP1; TIMP2). When normalized to the apoptotic cytokeratin-18 M30 neoepitope, HCV + ABs exhibited a more pronounced effect than HCV - ABs. In contrast, neither noningested ABs nor nucleic acids obtained from Huh7, Huh7 Con1+ or HepG2 cells triggered those AB-dependent effects. Both the engulfment of Huh7 Con1+ ABs and their effects were partially blocked by masking of phosphatidylserine with annexin V and completely inhibited by the class-A scavenger receptor ligand, polyinosinic acid. Our findings demonstrate that AB uptake stimulates HSCs and indicate that HCV infection leads to amplified fibrogenic mRNA expression and enhanced HSC activation.
Original language | English |
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Pages (from-to) | 760-767 |
Number of pages | 8 |
Journal | Journal of Viral Hepatitis |
Volume | 18 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2011 |
Externally published | Yes |
Keywords
- Con1
- Huh7 cells
- LX2 cells
- annexin V
- polyinosinic acid
- profibrotic genes