title: Inflammatory response of endothelial cells to hepatitis C virus recombinant envelope glycoprotein 2 protein exposure.
abstract: The hepatitis C virus (HCV) encodes approximately 10 different structural and non-structural proteins, including the envelope glycoprotein 2 (E2). HCV proteins, especially the envelope proteins, bind to cell receptors and can damage tissues. Endothelial inflammation is the most important determinant of fibrosis progression and, consequently, cirrhosis. The aim of this study was to evaluate and compare the inflammatory response of endothelial cells to two recombinant forms of the HCV E2 protein produced in different expression systems (Escherichia coli and Pichia pastoris). We observed the induction of cell death and the production of nitric oxide, hydrogen peroxide, interleukin-8 and vascular endothelial growth factor A in human umbilical vein endothelial cells (HUVECs) stimulated by the two recombinant E2 proteins. The E2-induced apoptosis of HUVECs was confirmed using the molecular marker PARP. The apoptosis rescue observed when the antioxidant N-acetylcysteine was used suggests that reactive oxygen species are involved in E2-induced apoptosis. We propose that these proteins are involved in the chronic inflammation caused by HCV.
authors.affiliation: Laboratório de Imunologia Clínica, Departamento de Análises Clínicas, Escola de Ciências Farmacêuticas, Bauru, SP, Brasil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Urbaczek
authors.affiliation: Laboratório de Imunologia Clínica, Departamento de Análises Clínicas, Escola de Ciências Farmacêuticas, Bauru, SP, Brasil.
authors.forename: Lívia Carolina de Abreu
authors.initials: LC
authors.lastname: Ribeiro
authors.affiliation: Departamento de Química, Faculdade de Ciências, Universidade Estadual Paulista Julio de Mesquita Filho, Bauru, SP, Brasil.
authors.forename: Valdecir Farias
authors.initials: VF
authors.lastname: Ximenes
authors.affiliation: Unidade de Parasitologia Médica e Microbiologia, Departamento de Parasitologia Médica, Instituto de Higiene e Medicina Tropcal, Universidade Nova de Lisboa, Lisboa, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Afonso
authors.affiliation: Laboratório de Imunologia Clínica, Departamento de Análises Clínicas, Escola de Ciências Farmacêuticas, Bauru, SP, Brasil.
authors.forename: Camila Tita
authors.initials: CT
authors.lastname: Nogueira
authors.affiliation: Departamento de Genética e Evolução, Universidade Federal de São Carlos, São Carlos, SP, Brasil.
authors.forename: Wesley Cardoso
authors.initials: WC
authors.lastname: Generoso
authors.affiliation: Grupo de Bioanalítica, Microfabricações e Separações, Departamento de Química e Física Molecular, Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brasil.
authors.forename: Juliana Vieira
authors.initials: JV
authors.lastname: Alberice
authors.affiliation: Escola de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Martina
authors.initials: M
authors.lastname: Rudnicki
authors.affiliation: Escola de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brasil.
authors.forename: Renila
authors.initials: R
authors.lastname: Ferrer
authors.affiliation: Laboratório de Imunologia Clínica, Departamento de Análises Clínicas, Escola de Ciências Farmacêuticas, Bauru, SP, Brasil.
authors.forename: Luiz Marcos da
authors.initials: LM
authors.lastname: Fonseca
authors.affiliation: Laboratório de Imunologia Clínica, Departamento de Análises Clínicas, Escola de Ciências Farmacêuticas, Bauru, SP, Brasil.
authors.forename: Paulo Inácio da
authors.initials: PI
authors.lastname: Costa
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001119:Arginase / Q000378:metabolism; D002470:Cell Survival; D004926:Escherichia coli / Q000378:metabolism; D005355:Fibrosis; D015870:Gene Expression / Q000235:genetics; D005818:Genetic Engineering / Q000379:methods; D005822:Genetic Vectors / Q000378:metabolism; D016174:Hepacivirus / Q000276:immunology / Q000378:metabolism*; D018936:Hepatitis C Antigens / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010843:Pichia / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism*
chemical_list: D018936:Hepatitis C Antigens; D016209:Interleukin-8; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; D009569:Nitric Oxide; D001119:Arginase