CREB is an essential transcription factor for prostaglandin E2 induced IL-23p19 (116.18)
| Autor: | Virginia Kocieda, Sabina Adhikary, Fran Emig, Doina Ganea |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 186:116.18-116.18 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.186.supp.116.18 |
| Popis: | We reported previously that PGE2 promotes IL-23p19 expression in dendritic cells (DC) treated with LPS. The effect is mediated through EP4 through the induction of cAMP. This study is focused on the signaling pathways involved in PGE1OH (an EP4 agonist)-induced p19 expression. EP4 activates adenylate cyclase and increases intracellular cAMP which leads to activation of PKA and EPAC. We found that adenylate cyclase, cAMP, and EPAC play a role in IL-23p19 induction. Using chemical inhibitors of PKA, PI3K, MAPK, and GSK3, we did not see a decrease in IL-23p19 expression. Previous studies reported the involvement of NFkB/c-Rel, ATF-2, SMAD-3 and AP-1 in p19 expression. Since two CRE-binding sites have been identified in the p19 promoter, we focused on CREB as a potential transcription factor activated by PGE1OH. Luciferase experiments including vectors containing mutated CRE sites and expressing dominant negative versions of CREB demonstrated the essential role CREB plays in IL-23p19 expression. In a transcription factor assay we found increased CREB binding activity in nuclear extracts from cells treated with PGE1OH. In addition, a ChIP assay confirmed CREB binding to the p19-promoter in the presence of PGE1OH. Overall, we identified CREB as a new transcription factor required for PGE1OH induction of IL-23p19 expression. |
| Databáze: | OpenAIRE |
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