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Article: A role for protein phosphatase 2A in regulating p38 mitogen activated protein kinase activation and tumor necrosis factor-alpha expression during influenza virus infection.

TitleA role for protein phosphatase 2A in regulating p38 mitogen activated protein kinase activation and tumor necrosis factor-alpha expression during influenza virus infection.
Authors
KeywordsProtein phosphatase 2A
Tumor necrosis factor-alpha
p38 mitogen activated protein kinase
Influenza virus
Issue Date2013
PublisherMolecular Diversity Preservation International. The Journal's web site is located at http://www.mdpi.org/ijms
Citation
International Journal of Molecular Sciences, 2013, v. 14 n. 4, p. 7327-7340 How to Cite?
AbstractInfluenza viruses of avian origin continue to pose pandemic threats to human health. Some of the H5N1 and H9N2 virus subtypes induce markedly elevated cytokine levels when compared with the seasonal H1N1 virus. We previously showed that H5N1/97 hyperinduces tumor necrosis factor (TNF)-alpha through p38 mitogen activated protein kinase (MAPK). However, the detailed mechanisms of p38MAPK activation and TNF-alpha hyperinduction following influenza virus infections are not known. Negative feedback regulations of cytokine expression play important roles in avoiding overwhelming production of proinflammatory cytokines. Here we hypothesize that protein phosphatases are involved in the regulation of cytokine expressions during influenza virus infection. We investigated the roles of protein phosphatases including MAPK phosphatase-1 (MKP-1) and protein phosphatase type 2A (PP2A) in modulating p38MAPK activation and downstream TNF-alpha expressions in primary human monocyte-derived macrophages (PBMac) infected with H9N2/G1 or H1N1 influenza virus. We demonstrate that H9N2/G1 virus activated p38MAPK and hyperinduced TNF-alpha production in PBMac when compared with H1N1 virus. H9N2/G1 induced PP2A activity in PBMac and, with the treatment of a PP2A inhibitor, p38MAPK phosphorylation and TNF-alpha production were further increased in the virus-infected macrophages. However, H9N2/G1 did not induce the expression of PP2A indicating that the activation of PP2A is not mediated by p38MAPK in virus-infected PBMac. On the other hand, PP2A may not be the targets of H9N2/G1 in the upstream of p38MAPK signaling pathways since H1N1 also induced PP2A activation in primary macrophages. Our results may provide new insights into the control of cytokine dysregulation.
Persistent Identifierhttp://hdl.handle.net/10722/164461
ISSN
2015 Impact Factor: 3.257
2015 SCImago Journal Rankings: 1.160
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLaw, AHYen_US
dc.contributor.authorTam, AHMen_US
dc.contributor.authorLee, DCWen_US
dc.contributor.authorLau, ASYen_US
dc.date.accessioned2012-09-20T07:59:57Z-
dc.date.available2012-09-20T07:59:57Z-
dc.date.issued2013en_US
dc.identifier.citationInternational Journal of Molecular Sciences, 2013, v. 14 n. 4, p. 7327-7340en_US
dc.identifier.issn1422-0067-
dc.identifier.urihttp://hdl.handle.net/10722/164461-
dc.description.abstractInfluenza viruses of avian origin continue to pose pandemic threats to human health. Some of the H5N1 and H9N2 virus subtypes induce markedly elevated cytokine levels when compared with the seasonal H1N1 virus. We previously showed that H5N1/97 hyperinduces tumor necrosis factor (TNF)-alpha through p38 mitogen activated protein kinase (MAPK). However, the detailed mechanisms of p38MAPK activation and TNF-alpha hyperinduction following influenza virus infections are not known. Negative feedback regulations of cytokine expression play important roles in avoiding overwhelming production of proinflammatory cytokines. Here we hypothesize that protein phosphatases are involved in the regulation of cytokine expressions during influenza virus infection. We investigated the roles of protein phosphatases including MAPK phosphatase-1 (MKP-1) and protein phosphatase type 2A (PP2A) in modulating p38MAPK activation and downstream TNF-alpha expressions in primary human monocyte-derived macrophages (PBMac) infected with H9N2/G1 or H1N1 influenza virus. We demonstrate that H9N2/G1 virus activated p38MAPK and hyperinduced TNF-alpha production in PBMac when compared with H1N1 virus. H9N2/G1 induced PP2A activity in PBMac and, with the treatment of a PP2A inhibitor, p38MAPK phosphorylation and TNF-alpha production were further increased in the virus-infected macrophages. However, H9N2/G1 did not induce the expression of PP2A indicating that the activation of PP2A is not mediated by p38MAPK in virus-infected PBMac. On the other hand, PP2A may not be the targets of H9N2/G1 in the upstream of p38MAPK signaling pathways since H1N1 also induced PP2A activation in primary macrophages. Our results may provide new insights into the control of cytokine dysregulation.-
dc.languageengen_US
dc.publisherMolecular Diversity Preservation International. The Journal's web site is located at http://www.mdpi.org/ijms-
dc.relation.ispartofInternational Journal of Molecular Sciencesen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectProtein phosphatase 2A-
dc.subjectTumor necrosis factor-alpha-
dc.subjectp38 mitogen activated protein kinase-
dc.subjectInfluenza virus-
dc.titleA role for protein phosphatase 2A in regulating p38 mitogen activated protein kinase activation and tumor necrosis factor-alpha expression during influenza virus infection.en_US
dc.typeArticleen_US
dc.identifier.emailLaw, AHY: lawanna@hkucc.hku.hken_US
dc.identifier.emailTam, AHM: tempo927@yahoo.com.hken_US
dc.identifier.emailLee, DCW: dcwlee@hku.hken_US
dc.identifier.emailLau, ASY: asylau@hku.hk-
dc.identifier.authorityLau, ASY=rp00474en_US
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3390/ijms14047327-
dc.identifier.pmid23549267-
dc.identifier.scopuseid_2-s2.0-84875984397-
dc.identifier.hkuros207522en_US
dc.identifier.volume14-
dc.identifier.issue4-
dc.identifier.spage7327-
dc.identifier.epage7340-
dc.identifier.isiWOS:000318017100037-
dc.publisher.placeSwitzerland-
dc.customcontrol.immutablejt 130412-

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