Inflammatory response of endothelial cells to hepatitis C virus recombinant envelope glycoprotein 2 protein exposure

Author(s):Show less -

Urbaczek, Ana Carolina ^[1] ; de Abreu Ribeiro, Livia Carolina ^[1] ; Ximenes, Valdecir Farias ^[2] ; Afonso, Ana ^{[3, 4, 5]} ; Nogueira, Camila Tita ^[1] ; Generoso, Wesley Cardoso ^[6] ; Alberice, Juliana Vieira ^[3] ; Rudnicki, Martina ^[7] ; Ferrer, Renila ^[7] ; da Fonseca, Luiz Marcos ^[1] ; da Costa, Paulo Iacio ^[1]

Affiliation

^[1] Univ Estadual Paulista, Fac Ciencias, Escola Ciencias Farmaceut, Dept Anal Clin, Lab Imunol Clin, Bauru, SP - Brazil

^[2] Univ Estadual Paulista, Fac Ciencias, Dept Quim, Bauru, SP - Brazil

^[3] Univ Sao Paulo, Inst Quim Sao Carlos, Dept Quim Fis Mol, Grp Bioanalit Microfabricacoes Separacoes, Sao Carlos, SP - Brazil

^[4] Univ Nova Lisboa, Inst Higiene & Med Tropcal, Dept Med Parasitol, Unidade Parasitol Med & Microbiol, P-1200 Lisbon - Portugal

^[5] Univ Fed Sao Carlos, Dept Morfol & Patol, BR-13560 Sao Carlos, SP - Brazil

^[6] Univ Fed Sao Carlos, Dept Genet & Evolucao, BR-13560 Sao Carlos, SP - Brazil

^[7] Univ Sao Paulo, Escola Ciencias Farmaceut, Sao Paulo - Brazil

• Document type: Journal article
• Source: Memórias do Instituto Oswaldo Cruz; v. 109, n. 6, p. 748-756, SEP 2014.
• Web of Science Citations: 7

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. (AU)