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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.
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TitleA role for protein phosphatase 2A in regulating p38 mitogen activated protein kinase activation and tumor necrosis factor-alpha expression during influenza virus infection.
 
AuthorsLaw, AHY1
Tam, AHM1
Lee, DCW1
Lau, ASY1
 
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
 
CitationInternational Journal of Molecular Sciences, 2013, v. 14 n. 4, p. 7327-7340 [How to Cite?]
DOI: http://dx.doi.org/10.3390/ijms14047327
 
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.
 
ISSN1422-0067
2013 Impact Factor: 2.339
2013 SCImago Journal Rankings: 0.776
 
DOIhttp://dx.doi.org/10.3390/ijms14047327
 
ISI Accession Number IDWOS:000318017100037
 
DC FieldValue
dc.contributor.authorLaw, AHY
 
dc.contributor.authorTam, AHM
 
dc.contributor.authorLee, DCW
 
dc.contributor.authorLau, ASY
 
dc.date.accessioned2012-09-20T07:59:57Z
 
dc.date.available2012-09-20T07:59:57Z
 
dc.date.issued2013
 
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.description.naturepublished_or_final_version
 
dc.identifier.citationInternational Journal of Molecular Sciences, 2013, v. 14 n. 4, p. 7327-7340 [How to Cite?]
DOI: http://dx.doi.org/10.3390/ijms14047327
 
dc.identifier.doihttp://dx.doi.org/10.3390/ijms14047327
 
dc.identifier.epage7340
 
dc.identifier.hkuros207522
 
dc.identifier.isiWOS:000318017100037
 
dc.identifier.issn1422-0067
2013 Impact Factor: 2.339
2013 SCImago Journal Rankings: 0.776
 
dc.identifier.issue4
 
dc.identifier.pmid23549267
 
dc.identifier.scopuseid_2-s2.0-84875984397
 
dc.identifier.spage7327
 
dc.identifier.urihttp://hdl.handle.net/10722/164461
 
dc.identifier.volume14
 
dc.languageeng
 
dc.publisherMolecular Diversity Preservation International. The Journal's web site is located at http://www.mdpi.org/ijms
 
dc.publisher.placeSwitzerland
 
dc.relation.ispartofInternational Journal of Molecular Sciences
 
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.
 
dc.typeArticle
 
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<contributor.author>Lau, ASY</contributor.author>
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<description.abstract>Influenza 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.</description.abstract>
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<subject>Protein phosphatase 2A</subject>
<subject>Tumor necrosis factor-alpha</subject>
<subject>p38 mitogen activated protein kinase</subject>
<subject>Influenza virus</subject>
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Author Affiliations
  1. The University of Hong Kong