Hepatocyte apoptotic bodies encasing nonstructural HCV proteins amplify hepatic stellate cell activation: Implications for chronic hepatitis C

R. K. Gieseler, G. Marquitan, M. Schlattjan, J. P. Sowa, L. P. Bechmann, J. Timm, M. Roggendorf, G. Gerken, S. L. Friedman, A. Canbay

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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 languageEnglish
Pages (from-to)760-767
Number of pages8
JournalJournal of Viral Hepatitis
Volume18
Issue number11
DOIs
StatePublished - Nov 2011

Keywords

  • Con1
  • Huh7 cells
  • LX2 cells
  • annexin V
  • polyinosinic acid
  • profibrotic genes

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