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• W2149705252 endingPage "1082" @default.
• W2149705252 startingPage "1069" @default.
• W2149705252 abstract "In this study, we investigated the role of ASK1 in PGN-induced C/EBPbeta activation and COX-2 expression in RAW 264.7 macrophages. The PGN-induced COX-2 expression was attenuated by the DNs of ASK1, JNK1, JNK2, a JNK inhibitor (SP600125), and an AP-1 inhibitor (curcumin). PGN caused ASK1 dephosphorylation time-dependently at Ser967, dissociation from the ASK1-14-3-3 complex, and subsequent ASK1 activation. In addition, PGN activated PP2A and suppression of PP2A by okadaic acid markedly inhibited PGN-induced ASK1 Ser967 dephosphorylation and COX-2 expression. PGN induced the activation of the JNK-AP-1 signaling cascade downstream of ASK1. PGN-increased C/EBPbeta expression and DNA-binding activity were inhibited by the ASK1-JNK-AP-1 signaling blockade. COX-2 promoter luciferase activity induced by PGN was attenuated in cells transfected with the COX-2 reporter construct possessing the C/EBP-binding site mutation. In addition, the ASK1-JNK-AP-1-C/EBPbeta cascade was activated in human peripheral mononuclear cells exposure to PGN. The TLR2 agonist Pam(3)CSK(4) was also shown to induce ASK1 Ser967 dephosphorylation, JNK and c-jun phosphorylation, C/EBPbeta activation, and COX-2 expression in RAW 264.7 macrophages. PGN-induced COX-2 promoter luciferase activity was prevented by selective inhibition of TLR2 and c-Jun in RAW 264.7 macrophages. Our data demonstrate that PGN might activate the TLR2-mediated PP2A-ASK1-JNK-AP-1-C/EBPbeta cascade and subsequent COX-2 expression in RAW 264.7 macrophages." @default.
• W2149705252 created "2016-06-24" @default.
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• W2149705252 date "2010-03-03" @default.
• W2149705252 modified "2023-10-17" @default.
• W2149705252 title "Apoptosis signal-regulating kinase 1 in peptidoglycan-induced COX-2 expression in macrophages" @default.
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• W2149705252 doi "https://doi.org/10.1189/jlb.1009668" @default.
• W2149705252 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20200402" @default.
• W2149705252 hasPublicationYear "2010" @default.
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