Enterovirus 71 modulates a COX-2/PGE2/cAMP-dependent viral replication in human neuroblastoma cells

Role of the c-Src/EGFR/p42/p44 MAPK/CREB signaling pathway

Wei Hsuan Tung, Hsi Lung Hsieh, I-Ta Lee, Chuen Mao Yang

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Enterovirus 71 (EV71) has been shown to induce cyclooxygenase-2 (COX-2) expression in human neuroblastoma SK-N-SH cells through the action of MAPKs, NF-KB, and AP-1. On the other hand, the transcription factor CREB has also been implicated in the expression of COX-2 in other cell lines. Here, we report that EV71-induced COX-2 expression and PGE2 production were both inhibited by pretreatment with the PKA inhibitor H89 or by transfection with CREB siRNA. In addition, EV71-induced COX-2 expression and c-Src/EGFR phosphorylation were both attenuated by transfection with c-Src siRNA or pretreatment with the inhibitors of c-Src (PP1) or EGF receptor (EGFR) (AG1478 and EGFR-neutralizing antibody). We also observed that EV71-induced p42/p44 MAPK phosphorylation was decreased following pretreatment with AG1478. Moreover, EV71-induced COX-2 expression was blocked by pretreatment with the p300 inhibitor GR343 or by transfection with p300 siRNA. Using immunoprecipitation and chromatin immunoprecipitation assays, we observed that EV71 stimulated the association of CREB and p300 with the COX-2 promoter region. Notably, we also demonstrated that EV71-induced COX-2 expression and PGE2 production promoted viral replication via cAMP signaling. In summary, this study demonstrates that EV71 activates the c-Src/EGFR/p42/p44 MAPK pathway in human SK-N-SH cell, which leads to the activation of CREB/p300, and stimulates COX-2 expression and PGE 2 release.

Original languageEnglish
Pages (from-to)559-570
Number of pages12
JournalJournal of Cellular Biochemistry
Volume112
Issue number2
DOIs
Publication statusPublished - Feb 1 2011
Externally publishedYes

Fingerprint

Mitogen-Activated Protein Kinase 3
Enterovirus
Mitogen-Activated Protein Kinase 1
Cyclooxygenase 2
Neuroblastoma
Epidermal Growth Factor Receptor
Dinoprostone
Small Interfering RNA
Transfection
Phosphorylation
Chromatin Immunoprecipitation
Transcription Factor AP-1
Prostaglandins E
Neutralizing Antibodies
Immunoprecipitation
Genetic Promoter Regions
Chromatin
Assays
Transcription Factors
Chemical activation

Keywords

  • COX-2
  • CREB
  • EGF receptor
  • EV71
  • neuroblastoma cells
  • PGE

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Enterovirus 71 modulates a COX-2/PGE2/cAMP-dependent viral replication in human neuroblastoma cells : Role of the c-Src/EGFR/p42/p44 MAPK/CREB signaling pathway. / Tung, Wei Hsuan; Hsieh, Hsi Lung; Lee, I-Ta; Yang, Chuen Mao.

In: Journal of Cellular Biochemistry, Vol. 112, No. 2, 01.02.2011, p. 559-570.

Research output: Contribution to journalArticle

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abstract = "Enterovirus 71 (EV71) has been shown to induce cyclooxygenase-2 (COX-2) expression in human neuroblastoma SK-N-SH cells through the action of MAPKs, NF-KB, and AP-1. On the other hand, the transcription factor CREB has also been implicated in the expression of COX-2 in other cell lines. Here, we report that EV71-induced COX-2 expression and PGE2 production were both inhibited by pretreatment with the PKA inhibitor H89 or by transfection with CREB siRNA. In addition, EV71-induced COX-2 expression and c-Src/EGFR phosphorylation were both attenuated by transfection with c-Src siRNA or pretreatment with the inhibitors of c-Src (PP1) or EGF receptor (EGFR) (AG1478 and EGFR-neutralizing antibody). We also observed that EV71-induced p42/p44 MAPK phosphorylation was decreased following pretreatment with AG1478. Moreover, EV71-induced COX-2 expression was blocked by pretreatment with the p300 inhibitor GR343 or by transfection with p300 siRNA. Using immunoprecipitation and chromatin immunoprecipitation assays, we observed that EV71 stimulated the association of CREB and p300 with the COX-2 promoter region. Notably, we also demonstrated that EV71-induced COX-2 expression and PGE2 production promoted viral replication via cAMP signaling. In summary, this study demonstrates that EV71 activates the c-Src/EGFR/p42/p44 MAPK pathway in human SK-N-SH cell, which leads to the activation of CREB/p300, and stimulates COX-2 expression and PGE 2 release.",
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