Involvement of PGE2 and the cAMP signalling pathway in the up-regulation of COX-2 and mPGES-1 expression in LPS-activated macrophages
| العنوان: | Involvement of PGE2 and the cAMP signalling pathway in the up-regulation of COX-2 and mPGES-1 expression in LPS-activated macrophages |
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| المؤلفون: | Inés C. Osma-García, Manuel Fresno, Manuel D. Díaz-Muñoz, Miguel A. Iñiguez |
| المساهمون: | UAM. Departamento de Biología Molecular, Comunidad de Madrid, Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares (España), European Commission, Ministerio de Ciencia e Innovación (España), Federación Española de Enfermedades Raras, Fundación Ramón Areces |
| المصدر: | Biblos-e Archivo. Repositorio Institucional de la UAM instname Digital.CSIC. Repositorio Institucional del CSIC |
| بيانات النشر: | Portland Press Ltd., 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Lipopolysaccharides, Transcriptional Activation, Transcription, Genetic, Prostaglandin E2 receptor, Lipid mediators, CREB, Biochemistry, Dinoprostone, Cell Line, Mice, chemistry.chemical_compound, Cyclo-oxygenase-2 (COX-2), Cyclic AMP, Animals, Promoter Regions, Genetic, Protein kinase A, Receptor, Molecular Biology, Transcription factor, Biología y Biomedicina, Prostaglandin-E Synthases, Inflammation, Regulation of gene expression, Forskolin, biology, Macrophages, EP receptors, Cell Biology, COX-2, mPGES-1, Molecular biology, Up-Regulation, Gene regulation, Intramolecular Oxidoreductases, chemistry, Cyclooxygenase 2, Lipid mediator, biology.protein, lipids (amino acids, peptides, and proteins), Signal transduction, E-prostanoid (EP) receptor, Signal Transduction, Microsomal prostaglandin E synthase 1 (mPGES-1) |
| الوصف: | PG (prostaglandin) E2 plays an important role in the modulation of the immune response and the inflammatory process. In the present study, we describe a PGE2 positive feedback for COX (cyclo oxygenase)-2 and mPGES-1 (microsomal PGES (PGE synthase)-1) expression in the macrophage cell line RAW 264.7. Our results show that PGE2 induces COX-2 and mPGES-1 expression, an effect mimicked by dbcAMP (dibutyryl-cAMP) or forskolin. Furthermore, the cAMP signalling pathway cooperates with LPS (lipopolysaccharide) in the induction of COX-2 and mPGES-1 transcriptional activation. Analysis of the involvement of PGE receptors (EPs (E-prostanoids)) showed that incubation with EP2 agonists up-regulated both COX2 and mPGES-1 mRNA levels. Moreover, EP2 receptor overexpression enhanced the transcriptional activation of COX2 and mPGES-1 promoters. This induction was repressed by the PKA (protein kinase A) inhibitor H89. Activation of the PGE2/EP2/PKA signalling pathway induced the phosphorylation of CREB (CRE (cAMP-response element)-binding protein) in macrophages and stimulated the specific binding of this transcription factor toCOX2 and mPGES-1 promoters. Deletion or mutation of potential CRE sites in both promoters diminished their transcriptional activity. In summary, the results of the present study demonstrate that activation of PKA/CREB signalling through the EP2 receptor by PGE2 plays a key role in the expression of COX-2 and mPGES-1 in activated macrophages Comunidad Autónoma de Madrid (CCG08-UAM/BIO-4299); the Cardiovascular Network (RECAVA) of the Instituto de Salud Carlos III (grant number RD06/0014/1013); the European EICOSANOX integrated project (grant number LSH-CT-2004-005033); the Ministerio deCiencia e Innovación; FEDER (grant numbers SAF2007-61716, SAF2010-18733 and BFU2007-62659/BMC, BFU2010-21055 (toM.A.I.); Fundación Ramón Areces |
| وصف الملف: | Application/pdf |
| تدمد: | 1470-8728 0264-6021 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ad7a1eb53d986f0dbbcc362cd22465eeTest https://doi.org/10.1042/bj20111052Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ad7a1eb53d986f0dbbcc362cd22465ee |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14708728 02646021 |
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