IFN-alpha5 mediates stronger Tyk2-stat-dependent activation and higher expression of 2',5'-oligoadenylate synthetase than IFN-alpha2 in liver cells

Interferon-alpha5 (IFN-alpha5) is the main IFN-alpha subtype expressed in the liver. Hepatitis C virus (HCV) infection is associated with low IFN-alpha5 mRNA levels, possibly reflecting an escape mechanism of the virus. In this work, we sought to compare IFN-alpha2 and IFN-alpha5 with respect to act...

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Detalles Bibliográficos
Autores: Larrea-Leoz, E. (Esther)|||/items/37a0521f-3293-4001-85d1-bc71241d8a83, Aldabe, R. (Rafael)|||/items/ef60614f-7fda-4565-bd52-0ace35b55292, Riezu-Boj, J.I. (José Ignacio)|||/items/87349e89-7360-4cdd-81be-2e8a6174b5f6, Guitart, A. (Anunciata)|||/items/5a339f00-6eb9-4dd4-a6a6-1b3c940f1695, Civeira, M.P. (María Pilar)|||/items/9aa9621a-63e5-4891-b19c-686ce6f2c29b, Prieto, J. (Jesús)|||/items/0d9c3dec-4a09-400d-8c83-23ece1096c71, Baixeras, E. (Elena)|||/items/e00d7081-5556-4469-aa4d-ecdfa76ac24f
Tipo de recurso: artículo
Fecha de publicación:2004
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/23014
Acceso en línea:https://hdl.handle.net/10171/23014
Access Level:acceso abierto
Palabra clave:2',5'-Oligoadenylate synthetase/metabolism
DNA-Binding proteins/metabolism
Hepatocytes/drug effects
Interferon-alpha/pharmacology
Protein-tyrosine kinases/metabolism
Trans-activators/metabolism
Hepatología
Descripción
Sumario:Interferon-alpha5 (IFN-alpha5) is the main IFN-alpha subtype expressed in the liver. Hepatitis C virus (HCV) infection is associated with low IFN-alpha5 mRNA levels, possibly reflecting an escape mechanism of the virus. In this work, we sought to compare IFN-alpha2 and IFN-alpha5 with respect to activation of early cell signaling cascades and induction of antiviral genes in the human hepatoma HepG2 and Huh7 cell lines. We found that the Tyr701 phosphorylation kinetics of Stat1 mediated by IFN stimulation was higher when cells were incubated with IFN-alpha5 than when using IFN-alpha2. Similarly, Tyr(1054/1055) phosphorylation kinetics of Tyk2 were more intense after exposure to IFN-alpha5 than when using IFN-alpha2. Concomitantly, Tyr705 phosphorylation of Stat3 was higher after stimulation with IFN-alpha5 than with IFN-alpha2. In parallel to these findings, the mRNA levels of the antiviral IFN-inducible gene 2',5'-oligoadenylate synthetase were higher in cell samples treated with IFN-alpha5 than with IFN-alpha2. These findings suggest that interaction of IFN-alpha5 and IFN-alpha2 subtypes with IFN type I receptor occurs differently, and this affects the intensity of expression of antiviral genes. In conclusion, our data show that in hepatocytic cells, IFN-alpha5 induces stronger signaling and higher expression of antiviral genes than IFN-alpha2. These data warrant clinical trials to evaluate the efficacy of IFN-alpha5 in chronic viral hepatitis.

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