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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.
Title | 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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Authors | |
Keywords | Protein phosphatase 2A Tumor necrosis factor-alpha p38 mitogen activated protein kinase Influenza virus |
Issue Date | 2013 |
Publisher | Molecular 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? |
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. |
Persistent Identifier | http://hdl.handle.net/10722/164461 |
ISSN | 2023 Impact Factor: 4.9 2023 SCImago Journal Rankings: 1.179 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Law, AHY | en_US |
dc.contributor.author | Tam, AHM | en_US |
dc.contributor.author | Lee, DCW | en_US |
dc.contributor.author | Lau, ASY | en_US |
dc.date.accessioned | 2012-09-20T07:59:57Z | - |
dc.date.available | 2012-09-20T07:59:57Z | - |
dc.date.issued | 2013 | en_US |
dc.identifier.citation | International Journal of Molecular Sciences, 2013, v. 14 n. 4, p. 7327-7340 | en_US |
dc.identifier.issn | 1422-0067 | - |
dc.identifier.uri | http://hdl.handle.net/10722/164461 | - |
dc.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. | - |
dc.language | eng | en_US |
dc.publisher | Molecular Diversity Preservation International. The Journal's web site is located at http://www.mdpi.org/ijms | - |
dc.relation.ispartof | International Journal of Molecular Sciences | en_US |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Protein phosphatase 2A | - |
dc.subject | Tumor necrosis factor-alpha | - |
dc.subject | p38 mitogen activated protein kinase | - |
dc.subject | Influenza virus | - |
dc.title | A 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.type | Article | en_US |
dc.identifier.email | Law, AHY: lawanna@hkucc.hku.hk | en_US |
dc.identifier.email | Tam, AHM: tempo927@yahoo.com.hk | en_US |
dc.identifier.email | Lee, DCW: dcwlee@hku.hk | en_US |
dc.identifier.email | Lau, ASY: asylau@hku.hk | - |
dc.identifier.authority | Lau, ASY=rp00474 | en_US |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.3390/ijms14047327 | - |
dc.identifier.pmid | 23549267 | - |
dc.identifier.scopus | eid_2-s2.0-84875984397 | - |
dc.identifier.hkuros | 207522 | en_US |
dc.identifier.volume | 14 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 7327 | - |
dc.identifier.epage | 7340 | - |
dc.identifier.isi | WOS:000318017100037 | - |
dc.publisher.place | Switzerland | - |
dc.customcontrol.immutable | jt 130412 | - |
dc.identifier.issnl | 1422-0067 | - |