Article: Induction of proinflammatory cytokines in primary human macrophages by influenza A virus (H5N1) is selectively regulated by IFN regulatory factor 3 and p38 MAPK

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TitleInduction of proinflammatory cytokines in primary human macrophages by influenza A virus (H5N1) is selectively regulated by IFN regulatory factor 3 and p38 MAPK
AuthorsHui, KPY1
Lee, SMY1
Cheung, CY1
Ng, IHY1
Poon, LLM1
Guan, Y1
Ip, NYY3
Lau, ASY1
Peiris, JSM1 2
Issue Date2009
PublisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org
CitationJournal Of Immunology, 2009, v. 182 n. 2, p. 1088-1098 [How to Cite?]
AbstractThe hyperinduction of proinflammatory cytokines and chemokines such as TNF-α, IFN-β, and CCL2/MCP-1 in primary human macrophages and respiratory epithelial cells by the highly pathogenic avian influenza H5N1 is believed to contribute to the unusual severity of human H5N1 disease. Here we show that TNF-α, IFN-β, and IFN-λ1 are the key mediators directly induced by the H5N1 virus in primary human macrophages. In comparison with human influenza (H1N1), the H5N1 virus more strongly activated IFN regulatory factor 3 (IRF3). IRF3 knockdown and p38 kinase inhibition separately and in combination led to a substantial reduction of IFN-β, IFN-λ1, and MCP-1 but only to a partial reduction of TNF-α. IRF3 translocation was independent of p38 kinase activity, indicating that IRF3 and p38 kinase are distinct pathways leading to cytokine production by H5N1 virus. We conclude that IRF3 and p38 kinase separately and predominantly contribute to H5N1-mediated induction of IFN-β, IFN-λ1, and MCP-1 but only partly control TNF-α induction. A more precise identification of the differences in the regulation of TNF-α and IFN-β could provide novel targets for the design of therapeutic strategies for severe human H5N1 influenza and also for treating other causes of acute respiratory distress syndrome. Copyright © 2009 by The American Association of Immunologists, Inc.
ISSN0022-1767
2011 Impact Factor: 5.788
2011 SCImago Journal Rankings: 1.099
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorHui, KPY
dc.contributor.authorLee, SMY
dc.contributor.authorCheung, CY
dc.contributor.authorNg, IHY
dc.contributor.authorPoon, LLM
dc.contributor.authorGuan, Y
dc.contributor.authorIp, NYY
dc.contributor.authorLau, ASY
dc.contributor.authorPeiris, JSM
dc.date.accessioned2010-05-31T03:49:19Z
dc.date.available2010-05-31T03:49:19Z
dc.date.issued2009
dc.description.abstractThe hyperinduction of proinflammatory cytokines and chemokines such as TNF-α, IFN-β, and CCL2/MCP-1 in primary human macrophages and respiratory epithelial cells by the highly pathogenic avian influenza H5N1 is believed to contribute to the unusual severity of human H5N1 disease. Here we show that TNF-α, IFN-β, and IFN-λ1 are the key mediators directly induced by the H5N1 virus in primary human macrophages. In comparison with human influenza (H1N1), the H5N1 virus more strongly activated IFN regulatory factor 3 (IRF3). IRF3 knockdown and p38 kinase inhibition separately and in combination led to a substantial reduction of IFN-β, IFN-λ1, and MCP-1 but only to a partial reduction of TNF-α. IRF3 translocation was independent of p38 kinase activity, indicating that IRF3 and p38 kinase are distinct pathways leading to cytokine production by H5N1 virus. We conclude that IRF3 and p38 kinase separately and predominantly contribute to H5N1-mediated induction of IFN-β, IFN-λ1, and MCP-1 but only partly control TNF-α induction. A more precise identification of the differences in the regulation of TNF-α and IFN-β could provide novel targets for the design of therapeutic strategies for severe human H5N1 influenza and also for treating other causes of acute respiratory distress syndrome. Copyright © 2009 by The American Association of Immunologists, Inc.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationJournal Of Immunology, 2009, v. 182 n. 2, p. 1088-1098 [How to Cite?]
dc.identifier.epage1098
dc.identifier.hkuros159182
dc.identifier.issn0022-1767
2011 Impact Factor: 5.788
2011 SCImago Journal Rankings: 1.099
dc.identifier.issue2
dc.identifier.scopuseid_2-s2.0-60549113990
dc.identifier.spage1088
dc.identifier.urihttp://hdl.handle.net/10722/59399
dc.identifier.volume182
dc.languageeng
dc.publisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org
dc.publisher.placeUnited States
dc.relation.ispartofJournal of Immunology
dc.relation.referencesReferences in Scopus
dc.titleInduction of proinflammatory cytokines in primary human macrophages by influenza A virus (H5N1) is selectively regulated by IFN regulatory factor 3 and p38 MAPK
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. HKU-Pasteur Research Centre
  3. Hong Kong University of Science and Technology