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EV71 induces COX‐2 expression and PGE 2 synthesis through c‐Src/EGFR/p42/p44 MAPK/CREB in SK‐N‐SH cells
Author(s) -
Tung WeiHsuan,
Yang ChuenMao
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.963.4
Subject(s) - creb , mapk/erk pathway , phosphorylation , chromatin immunoprecipitation , transfection , immunoprecipitation , protein kinase b , chemistry , microbiology and biotechnology , cancer research , biology , gene expression , transcription factor , promoter , biochemistry , gene
EV71 has been shown to induce cyclooxygenase‐2 (COX‐2) expression through MAPKs, NF‐κB, and AP‐1 in SK‐N‐SH cells. CREB has also been shown to be implicated in the expression of COX‐2. Here, we reported that EV71 induced COX‐2 expression and PGE 2 production, which were inhibited by pretreatment with the inhibitor of PKA (H89) and transfection with CREB siRNA. In addition, EV71‐stimulated c‐Src and EGFR phosphorylation and COX‐2 expression were attenuated by pretreatment with the inhibitors of c‐Src (PP1), EGFR (AG1478), or EGFR neutralized antibody. EV71‐stimulated Akt and p42/p44 MAPK phosphorylation were diminished by pretreatment with AG1478. Morever, we found that EV71 regulated CREB activation in a p42/p44 MAPK‐dependent manner. EV71‐induced COX‐2 expression was also blocked by pretreatment with the inhibitor of p300 (GR343) or transfection with p300 siRNA. EV71‐stimulated the association of CREB and p300 with COX‐2 promoter region was further confirmed by immunoprecipitation and chromatin immunoprecipitation assays. These results demonstrated that EV71‐induced CREB phosphorylation was mediated through the c‐Src/EGFR/p42/p44 MAPK pathway, in turn initiated the activation of p300, and ultimately induced COX‐2 expression and PGE 2 production in SK‐N‐SH cells.