Mechanism of hepatitis c virus-like particle-induced apoptosis in huvec

N. Munshi, R. K. Ganju, T. Jake Liang, M. J. Koziel, J. E. Groopman

Research output: Contribution to journalArticle

Abstract

Hepatitis C virus (HCV) infection causes inflammation of liver endothelium which contributes to the pathogenesis of chronic hepatitis. The mechanism of this endothelitis is not understood, since the virus does not appear to productively infect endothelial cells. We hypothesized an innocent bystander mechanism related to HCV proteins, and investigated whether the binding of HCV particles to human endothelium induced functioi ,al changes in the cells. Exposure of human vascular endothelial cells (HUVEC) to hepatitis C virus-like particles (HCV-LP) resulted in increased EL-8 production and induction of apoptosis. This programmed cell death appeared to be mediated by the Fas/Fas-L pathway as neutralizing antibodies for Fas and Fas-L significantly protected HUVEC against HCV-LP induced apoptosis. Treatment of HUVEC with HCV particles also enhanced Fas-L expression in these cells and augmented caspase-3 activation. This was confirmed by using a specific caspase-3 inhibitor, Z-DEVD-FMK. Neutralizing antibody to I ie CD81 receptor showed that it participated in the HCV particle induced apoptosis of endothelial cells. Release of interleukin-8 did not appear to involve the CD81 receptor, and IL-8 did not modulate apoptosis as shown by blocking its cognate receptors on HUVEC. These results suggest that HCV envelope proteins can trigger the release of inflammatory chemokines and endothelial apoptosis, and may explain the pathological finding of endothelitis.

Original languageEnglish (US)
JournalBlood
Volume96
Issue number11 PART I
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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    Munshi, N., Ganju, R. K., Jake Liang, T., Koziel, M. J., & Groopman, J. E. (2000). Mechanism of hepatitis c virus-like particle-induced apoptosis in huvec. Blood, 96(11 PART I).