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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

TitleInduction of proinflammatory cytokines in primary human macrophages by influenza A virus (H5N1) is selectively regulated by IFN regulatory factor 3 and p38 MAPK
Authors
Issue Date2009
PublisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.org
Citation
Journal 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.
Persistent Identifierhttp://hdl.handle.net/10722/59399
ISSN
2014 Impact Factor: 4.922
2014 SCImago Journal Rankings: 3.031
References

 

DC FieldValueLanguage
dc.contributor.authorHui, KPYen_HK
dc.contributor.authorLee, SMYen_HK
dc.contributor.authorCheung, CYen_HK
dc.contributor.authorNg, IHYen_HK
dc.contributor.authorPoon, LLMen_HK
dc.contributor.authorGuan, Yen_HK
dc.contributor.authorIp, NYYen_HK
dc.contributor.authorLau, ASYen_HK
dc.contributor.authorPeiris, JSMen_HK
dc.date.accessioned2010-05-31T03:49:19Z-
dc.date.available2010-05-31T03:49:19Z-
dc.date.issued2009en_HK
dc.identifier.citationJournal Of Immunology, 2009, v. 182 n. 2, p. 1088-1098en_HK
dc.identifier.issn0022-1767en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59399-
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.en_HK
dc.languageengen_HK
dc.publisherAmerican Association of Immunologists. The Journal's web site is located at http://www.jimmunol.orgen_HK
dc.relation.ispartofJournal of Immunologyen_HK
dc.titleInduction of proinflammatory cytokines in primary human macrophages by influenza A virus (H5N1) is selectively regulated by IFN regulatory factor 3 and p38 MAPKen_HK
dc.typeArticleen_HK
dc.identifier.emailLee, SMY: suki@hku.hken_HK
dc.identifier.emailCheung, CY: chungey@hkucc.hku.hken_HK
dc.identifier.emailPoon, LLM: llmpoon@hkucc.hku.hken_HK
dc.identifier.emailGuan, Y: yguan@hkucc.hku.hken_HK
dc.identifier.emailLau, ASY: asylau@hku.hken_HK
dc.identifier.emailPeiris, JSM: malik@hkucc.hku.hken_HK
dc.identifier.authorityLee, SMY=rp01536en_HK
dc.identifier.authorityCheung, CY=rp00404en_HK
dc.identifier.authorityPoon, LLM=rp00484en_HK
dc.identifier.authorityGuan, Y=rp00397en_HK
dc.identifier.authorityLau, ASY=rp00474en_HK
dc.identifier.authorityPeiris, JSM=rp00410en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.scopuseid_2-s2.0-60549113990en_HK
dc.identifier.hkuros159182en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-60549113990&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume182en_HK
dc.identifier.issue2en_HK
dc.identifier.spage1088en_HK
dc.identifier.epage1098en_HK
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHui, KPY=24492032000en_HK
dc.identifier.scopusauthoridLee, SMY=35435155600en_HK
dc.identifier.scopusauthoridCheung, CY=7202061836en_HK
dc.identifier.scopusauthoridNg, IHY=8671050800en_HK
dc.identifier.scopusauthoridPoon, LLM=7005441747en_HK
dc.identifier.scopusauthoridGuan, Y=7202924055en_HK
dc.identifier.scopusauthoridIp, NYY=7005756760en_HK
dc.identifier.scopusauthoridLau, ASY=7202626202en_HK
dc.identifier.scopusauthoridPeiris, JSM=7005486823en_HK

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