ERK activation is required for PGE2-induced MMP-9 production in bone-morrow derived DCs (112.23)
| Autor: | Jui-Hung Yen, Virginia Kocieda, Doina Ganea |
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| Rok vydání: | 2011 |
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| Zdroj: | The Journal of Immunology. 186:112.23-112.23 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.186.supp.112.23 |
| Popis: | Dendritic Cells (DCs) play an important role in the initiation of the immune response. Immature DCs take up antigen, mature and migrate to the regional lymph nodes where they activate antigen-specific naïve T cells. Prostaglandins such as PGE2 are essential for the migration of DCs to lymph nodes. Matrix metalloproteinases (MMPs) play an essential role in DC migration, through the degradation of extracellular matrix (ECM) and basement membranes. MMP2, and particularly MMP9, are essential for dendritic cell migration in vitro, as well as in vivo to the draining lymph nodes. In this study, we show that PGE2-induced MMP9 expression is mediated through the EP2/EP4-cAMP-PKA/PI3K-ERK signaling pathway. EP2 and EP4 receptors as well as cAMP analog mimic the effect of PGE2 to upregulate MMP-9. In the presence of PKA, PI3K or ERK inhibitors, PGE2-induced MMP-9 production is abolished. Furthermore, PGE2-induced c-Fos expression mediated through ERK activation is required for the binding of AP-1 transcription factor to the MMP-9 promoter. In the presence of ERK inhibitors, PGE2-induced AP-1 binding is abrogated. Our results describe a new molecular mechanism for the effect of PGE on MMP-9 production in DCs, which could lead to a new therapeutic approach by using ERK inhibitors to regulate DC migration. |
| Databáze: | OpenAIRE |
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