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Antibodies against dengue virus nonstructural protein-1 induce heme oxygenase-1 via a redox-dependent pathway in human endothelial cells.
Free Radic Biol Med. 2013 Jan; 54:85-92.FR

Abstract

Heme oxygenase (HO)-1, the inducible isoform of the first and rate-limiting enzyme of heme degradation, affords anti-inflammatory protection via its cell-type-specific effects in endothelial cells (ECs). In dengue hemorrhagic fever (DHF), which is the life-threatening form of dengue virus (DV) infection, endothelial interactions of cross-reactive antibodies against the DV nonstructural glycoprotein-1 (NS1) are associated with endothelial dysfunction. In this study, we investigated whether anti-NS1 antibodies might regulate HO-1 gene expression in human ECs. Serum from DHF patients with high anti-NS1 titers and a monoclonal anti-NS1 antibody upregulated HO-1 gene expression in human umbilical vein ECs, which was blocked by purified NS1 antigen. Immunoprecipitation studies showed that anti-NS1 antibodies specifically bound to the oxidoreductase protein disulfide isomerase (PDI) on ECs. Moreover, anti-NS1-mediated HO-1 induction was reduced by inhibition of PDI enzyme activity. Reactive oxygen species, which were generated by NADPH oxidase and in turn activated the phosphatidylinositol 3-kinase (PI3K)/Akt cascade, were involved in this upregulation of HO-1 gene expression. Finally, apoptosis of ECs caused by anti-NS1 antibodies was increased by pharmacological inhibition of HO-1 enzyme activity. In conclusion, HO-1 gene expression is upregulated by anti-NS1 antibodies via activation of a redox-dependent PDI/PI3K/Akt-mediated pathway in human ECs.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Immenschuh S
Institute for Transfusion Medicine, Hannover Medical School, 30625 Hannover, Germany. Immenschuh.Stephan@mh-hannover.de
Rahayu P
No affiliation info available
Bayat B
No affiliation info available
Saragih H
No affiliation info available
Rachman A
No affiliation info available
Santoso S
No affiliation info available

MeSH

Antibodies, ViralApoptosisCells, CulturedDengueDengue VirusGene Expression RegulationHeme Oxygenase-1Human Umbilical Vein Endothelial CellsHumansOxidation-ReductionPhosphatidylinositol 3-KinasesProtein Disulfide Reductase (Glutathione)Reactive Oxygen SpeciesSignal TransductionViral Nonstructural Proteins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23103292

Citation

Immenschuh, Stephan, et al. "Antibodies Against Dengue Virus Nonstructural Protein-1 Induce Heme Oxygenase-1 Via a Redox-dependent Pathway in Human Endothelial Cells." Free Radical Biology & Medicine, vol. 54, 2013, pp. 85-92.
Immenschuh S, Rahayu P, Bayat B, et al. Antibodies against dengue virus nonstructural protein-1 induce heme oxygenase-1 via a redox-dependent pathway in human endothelial cells. Free Radic Biol Med. 2013;54:85-92.
Immenschuh, S., Rahayu, P., Bayat, B., Saragih, H., Rachman, A., & Santoso, S. (2013). Antibodies against dengue virus nonstructural protein-1 induce heme oxygenase-1 via a redox-dependent pathway in human endothelial cells. Free Radical Biology & Medicine, 54, 85-92. https://doi.org/10.1016/j.freeradbiomed.2012.10.551
Immenschuh S, et al. Antibodies Against Dengue Virus Nonstructural Protein-1 Induce Heme Oxygenase-1 Via a Redox-dependent Pathway in Human Endothelial Cells. Free Radic Biol Med. 2013;54:85-92. PubMed PMID: 23103292.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antibodies against dengue virus nonstructural protein-1 induce heme oxygenase-1 via a redox-dependent pathway in human endothelial cells. AU - Immenschuh,Stephan, AU - Rahayu,Puji, AU - Bayat,Behnat, AU - Saragih,Hendry, AU - Rachman,Andhika, AU - Santoso,Sentot, Y1 - 2012/10/26/ PY - 2012/07/06/received PY - 2012/10/11/revised PY - 2012/10/18/accepted PY - 2012/10/30/entrez PY - 2012/10/30/pubmed PY - 2013/7/10/medline SP - 85 EP - 92 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 54 N2 - Heme oxygenase (HO)-1, the inducible isoform of the first and rate-limiting enzyme of heme degradation, affords anti-inflammatory protection via its cell-type-specific effects in endothelial cells (ECs). In dengue hemorrhagic fever (DHF), which is the life-threatening form of dengue virus (DV) infection, endothelial interactions of cross-reactive antibodies against the DV nonstructural glycoprotein-1 (NS1) are associated with endothelial dysfunction. In this study, we investigated whether anti-NS1 antibodies might regulate HO-1 gene expression in human ECs. Serum from DHF patients with high anti-NS1 titers and a monoclonal anti-NS1 antibody upregulated HO-1 gene expression in human umbilical vein ECs, which was blocked by purified NS1 antigen. Immunoprecipitation studies showed that anti-NS1 antibodies specifically bound to the oxidoreductase protein disulfide isomerase (PDI) on ECs. Moreover, anti-NS1-mediated HO-1 induction was reduced by inhibition of PDI enzyme activity. Reactive oxygen species, which were generated by NADPH oxidase and in turn activated the phosphatidylinositol 3-kinase (PI3K)/Akt cascade, were involved in this upregulation of HO-1 gene expression. Finally, apoptosis of ECs caused by anti-NS1 antibodies was increased by pharmacological inhibition of HO-1 enzyme activity. In conclusion, HO-1 gene expression is upregulated by anti-NS1 antibodies via activation of a redox-dependent PDI/PI3K/Akt-mediated pathway in human ECs. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/23103292/Antibodies_against_dengue_virus_nonstructural_protein_1_induce_heme_oxygenase_1_via_a_redox_dependent_pathway_in_human_endothelial_cells_ DB - PRIME DP - Unbound Medicine ER -