Prostaglandin E2 induces matrix metalloproteinase 9 expression in dendritic cells through two independent signaling pathways leading to activator protein 1 (AP-1) activation.
J Biol Chem
; 286(45): 38913-23, 2011 Nov 11.
Article
em En
| MEDLINE
| ID: mdl-21940623
ABSTRACT
Dendritic Cells (DCs) play an important role in the initiation of the immune response by migrating to regional lymph nodes and presenting antigen processed at the inflammatory site to antigen-specific naïve T cells. Prostaglandin E2 (PGE2) has been reported to play an essential role in DC migration. We reported previously that PGE2 induces matrix metalloproteinase 9 (MMP-9) expression in DCs and that PGE2-induced MMP-9 is required for DC migration in vivo and in vitro. In this study, we investigated the signaling mechanisms involved in PGE2-induced MMP-9 expression in DCs. We show that PGE2-induced MMP-9 expression is mediated primarily through the EP2/EP4 â cAMP â protein kinase A (PKA)/PI3K â ERK signaling pathway, leading to c-Fos expression, and through JNK-mediated activation of c-Jun in a PKA/PI3K/ERK-independent manner. EP2 and EP4 receptor agonists, as well as cAMP analogs, mimic the up-regulation of MMP-9 by PGE2. PKA, PI3K, and ERK inhibitors abolished PGE2- and cAMP-induced c-Fos and MMP-9 up-regulation, and ERK activation was required for the binding of activator protein 1 (AP-1) transcription factor to the MMP-9 promoter. Our results describe a new molecular mechanism for the effect of PGE2 on MMP-9 production in DCs that could lead to future therapeutic approaches using ERK inhibitors to regulate DC migration.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
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Dinoprostona
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Regulação para Cima
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Fator de Transcrição AP-1
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Metaloproteinase 9 da Matriz
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Sistema de Sinalização das MAP Quinases
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos