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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología hepatitis virales > DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista >

A recombinant adenovirus encoding hepatitis C virus core and E1 proteins protects mice against cytokine-induced liver damage
Authors: Lasarte, J.J. (Juan José)
Sarobe, P. (Pablo)
Boya, P. (Patricia)
Casares, N. (Noelia)
Arribillaga, L. (Laura)
Lopez-Diaz-de-Cerio, A. (Ascensión)
Gorraiz, M. (Marta)
Borras-Cuesta, F. (Francisco)
Prieto, J. (Jesús)
Keywords: Adenoviridae/genetics
Cytokines/physiology
Gene Expression/physiology
Hepacivirus/genetics
Liver Diseases/prevention & control
Issue Date: 2003
Publisher: Wiley-Blackwell
Publisher version: http://dx.doi.org/10.1053/jhep.2003.50073
ISSN: 0270-9139
Citation: Lasarte JJ, Sarobe P, Boya P, Casares N, Arribillaga L, de Cerio AL, et al. A recombinant adenovirus encoding hepatitis C virus core and E1 proteins protects mice against cytokine-induced liver damage. Hepatology 2003 Feb;37(2):461-470.
Abstract
Hepatitis C virus (HCV) infection has a strong tendency to evolve to chronicity despite up-regulation of proapoptotic cytokines in the inflamed liver. The mechanisms responsible for persistent viral replication in this inflammatory environment are obscure. It is conceivable that viral replication would be facilitated if the infected hepatocytes are rendered resistant to cytokine-induced cytotoxicity. In this study, we investigated if an adenovirus encoding HCV core and E1 (RAdCE1) could reduce liver cell injury in different in vivo models of cytokine-mediated hepatotoxicity in mice. We show that RAdCE1 markedly attenuates hepatocellular apoptosis and the increase in serum transaminase levels after concanavalin A (con A) challenge. This protective effect is accompanied by an inhibition of nuclear translocation of nuclear factor kappaB (NF-kappaB); reduced expression of inducible nitric oxide synthase (iNOS); decreased hepatic messenger RNA levels of chemokines macrophage inflammatory protein 2 (MIP-2), monocyte chemoattractant protein 1 (MCP-1), and interferon-inducible protein 10 (IP-10); and abrogation of liver leukocyte infiltration. RAdCE1 also causes a reduction in serum transaminase levels and inhibits hepatocellular apoptosis in mice given tumor necrosis factor (TNF)-alpha plus D-galactosamine. In conclusion, HCV structural antigens can protect liver cells against the proapoptotic effects of proinflammatory cytokines. The antiapoptotic status of infected liver cells may represent a mechanism favoring viral persistence. Our findings also suggest that, in chronic hepatitis C, the burden of hepatocellular damage mainly affects noninfected liver cells.
Permanent link: http://hdl.handle.net/10171/20609
Appears in Collections:DA - CIMA - Oncología - Inmunoterapia - Artículos de Revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología experimental - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista

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