Crosstalk between coagulation and inflammation during Dengue virus infection

Alejandra Huerta-Zepeda; Carlos Cabello-Gutiérrez; Jorge Cime-Castillo; Verónica Monroy-Martínez; Maria Eugenia Manjarrez-Zavala; Margarita Gutiérrez-Rodríguez; Raú Izaguirre; Blanca H. Ruiz-Ordaz

doi:10.1160/TH07-08-0483

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 99(05): 936-943
DOI: 10.1160/TH07-08-0483

Wound Healing and Inflammation/Infection

Schattauer GmbH

Crosstalk between coagulation and inflammation during Dengue virus infection

Alejandra Huerta-Zepeda

¹Departamento de Biología Molecular y Biotecnología. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, UNAM, México D.F., Mexico

,

Carlos Cabello-Gutiérrez

¹Departamento de Biología Molecular y Biotecnología. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, UNAM, México D.F., Mexico

,

Jorge Cime-Castillo

¹Departamento de Biología Molecular y Biotecnología. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, UNAM, México D.F., Mexico

,

Verónica Monroy-Martínez

¹Departamento de Biología Molecular y Biotecnología. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, UNAM, México D.F., Mexico

,

Maria Eugenia Manjarrez-Zavala

²Departamento de Virología, Instituto Nacional de Enfermedades Respiratorias, México D.F., México

,

Margarita Gutiérrez-Rodríguez

³Departamento de Bioquímica, Hospital de Especialidades, Centro Médico Siglo XXI, IMSS, México D.F., México

,

Raú Izaguirre

⁴Departamento de Hematología, Hospital de Cardiología “Ignacio Chávez” SSA, México D.F., México

,

Blanca H. Ruiz-Ordaz

¹Departamento de Biología Molecular y Biotecnología. Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, UNAM, México D.F., Mexico

› Author Affiliations

Abstract

Summary

Dengue fever is the most prevalent viral disease transmitted by vectors (Aedes aegypti, Aedes albopictus) in worldwide. More than 100 million cases occur annually with a mortality rate of 5% and no safe vaccine is available. The pathogenesis of Dengue, where host and viral factors participate in the establishment of Dengue haemorrhagic fever (DHF) and Dengue shock syndrome (DSS) remains unresolved. Clinical observations have revealed significant abnormalities in coagulation and inflammation systems, with increased levels of tissue factor (TF) and the chemokine IL-8, correlating with the severity of the disease and implicating damage to endothelial vascular cells (EVC). Here we present novel insights concerning the crosstalk between the regulatory signaling pathways of the coagulation-inflammation processes, during Dengue virus (DV) infection of EVC. We found that DV up-regulates Protease Activated receptor type-1 (inflammation) and TF (coagulation) receptors, via the phosphorylation of p38 and ERK1/2 MAPKs, which favor the activation of NF-κB transcription factor. This induces pro-inflammatory (IL-8) or pro-adhesive (VCAM-1) gene expression which may lead to EVC activation. The elucidation of the basic principles that signal these processes has important implications for the design of new therapeutic strategies for DHF/DSS.

keywords

Dengue virus - tissue factor - PAR-1 - endothelial cell - crosstalk - coagulation-inflammation

Full Text

References

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