Inhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation.

Influenza A virus pandemics and emerging anti-viral resistance highlight the urgent need for novel generic pharmacological strategies that reduce both viral replication and lung inflammation. We investigated whether the primary enzymatic source of inflammatory cell ROS (reactive oxygen species), Nox...

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Autores principales:	Ross Vlahos, John Stambas, Steven Bozinovski, Brad R S Broughton, Grant R Drummond, Stavros Selemidis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/89a65053227b431bbd150918f57388f5
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spelling	oai:doaj.org-article:89a65053227b431bbd150918f57388f52021-11-18T06:03:39ZInhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation.1553-73661553-737410.1371/journal.ppat.1001271https://doaj.org/article/89a65053227b431bbd150918f57388f52011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21304882/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Influenza A virus pandemics and emerging anti-viral resistance highlight the urgent need for novel generic pharmacological strategies that reduce both viral replication and lung inflammation. We investigated whether the primary enzymatic source of inflammatory cell ROS (reactive oxygen species), Nox2-containing NADPH oxidase, is a novel pharmacological target against the lung inflammation caused by influenza A viruses. Male WT (C57BL/6) and Nox2(-/y) mice were infected intranasally with low pathogenicity (X-31, H3N2) or higher pathogenicity (PR8, H1N1) influenza A virus. Viral titer, airways inflammation, superoxide and peroxynitrite production, lung histopathology, pro-inflammatory (MCP-1) and antiviral (IL-1β) cytokines/chemokines, CD8(+) T cell effector function and alveolar epithelial cell apoptosis were assessed. Infection of Nox2(-/y) mice with X-31 virus resulted in a significant reduction in viral titers, BALF macrophages, peri-bronchial inflammation, BALF inflammatory cell superoxide and lung tissue peroxynitrite production, MCP-1 levels and alveolar epithelial cell apoptosis when compared to WT control mice. Lung levels of IL-1β were ∼3-fold higher in Nox2(-/y) mice. The numbers of influenza-specific CD8+D(b)NP(366)+ and D(b)PA(224)+ T cells in the BALF and spleen were comparable in WT and Nox2(-/y) mice. In vivo administration of the Nox2 inhibitor apocynin significantly suppressed viral titer, airways inflammation and inflammatory cell superoxide production following infection with X-31 or PR8. In conclusion, these findings indicate that Nox2 inhibitors have therapeutic potential for control of lung inflammation and damage in an influenza strain-independent manner.Ross VlahosJohn StambasSteven BozinovskiBrad R S BroughtonGrant R DrummondStavros SelemidisPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 2, p e1001271 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Ross Vlahos John Stambas Steven Bozinovski Brad R S Broughton Grant R Drummond Stavros Selemidis Inhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation.
description	Influenza A virus pandemics and emerging anti-viral resistance highlight the urgent need for novel generic pharmacological strategies that reduce both viral replication and lung inflammation. We investigated whether the primary enzymatic source of inflammatory cell ROS (reactive oxygen species), Nox2-containing NADPH oxidase, is a novel pharmacological target against the lung inflammation caused by influenza A viruses. Male WT (C57BL/6) and Nox2(-/y) mice were infected intranasally with low pathogenicity (X-31, H3N2) or higher pathogenicity (PR8, H1N1) influenza A virus. Viral titer, airways inflammation, superoxide and peroxynitrite production, lung histopathology, pro-inflammatory (MCP-1) and antiviral (IL-1β) cytokines/chemokines, CD8(+) T cell effector function and alveolar epithelial cell apoptosis were assessed. Infection of Nox2(-/y) mice with X-31 virus resulted in a significant reduction in viral titers, BALF macrophages, peri-bronchial inflammation, BALF inflammatory cell superoxide and lung tissue peroxynitrite production, MCP-1 levels and alveolar epithelial cell apoptosis when compared to WT control mice. Lung levels of IL-1β were ∼3-fold higher in Nox2(-/y) mice. The numbers of influenza-specific CD8+D(b)NP(366)+ and D(b)PA(224)+ T cells in the BALF and spleen were comparable in WT and Nox2(-/y) mice. In vivo administration of the Nox2 inhibitor apocynin significantly suppressed viral titer, airways inflammation and inflammatory cell superoxide production following infection with X-31 or PR8. In conclusion, these findings indicate that Nox2 inhibitors have therapeutic potential for control of lung inflammation and damage in an influenza strain-independent manner.
format	article
author	Ross Vlahos John Stambas Steven Bozinovski Brad R S Broughton Grant R Drummond Stavros Selemidis
author_facet	Ross Vlahos John Stambas Steven Bozinovski Brad R S Broughton Grant R Drummond Stavros Selemidis
author_sort	Ross Vlahos
title	Inhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation.
title_short	Inhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation.
title_full	Inhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation.
title_fullStr	Inhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation.
title_full_unstemmed	Inhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation.
title_sort	inhibition of nox2 oxidase activity ameliorates influenza a virus-induced lung inflammation.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/89a65053227b431bbd150918f57388f5
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Inhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation.

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