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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-1-26
pubmed:abstractText
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-?B, 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 PGE(2) 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 PGE(2) 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1097-4644
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
112
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
559-70
pubmed:meshHeading
pubmed-meshheading:21268077-Blotting, Western, pubmed-meshheading:21268077-Cell Line, Tumor, pubmed-meshheading:21268077-Chromatin Immunoprecipitation, pubmed-meshheading:21268077-Cyclic AMP, pubmed-meshheading:21268077-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:21268077-Cyclooxygenase 2, pubmed-meshheading:21268077-Dinoprostone, pubmed-meshheading:21268077-Enterovirus A, Human, pubmed-meshheading:21268077-Genes, src, pubmed-meshheading:21268077-Humans, pubmed-meshheading:21268077-Immunoprecipitation, pubmed-meshheading:21268077-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:21268077-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:21268077-Neuroblastoma, pubmed-meshheading:21268077-Phosphorylation, pubmed-meshheading:21268077-Protein Binding, pubmed-meshheading:21268077-Receptor, Epidermal Growth Factor, pubmed-meshheading:21268077-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:21268077-Virus Replication
pubmed:year
2011
pubmed:articleTitle
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.
pubmed:affiliation
Department of Physiology and Pharmacology, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't