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Registro de acceso cerrado Angiotensin II differentially modulates cyclooxygenase-2, microsomal prostaglandin E2 synthase-1 and prostaglandin I2 synthase expression in adventitial fibroblasts exposed to inflammatory stimuli
|Autor :||Galán, M.|
García-Redondo, A. B.
Alonso, M. J.
Beltrán, A. E.
|Fecha de publicación :||2011|
|Editor:||Lippincott Williams & Wilkins|
|Citación :||Journal of Hypertension 29(3): 529-536 (2011)|
|Resumen:||[Aims]: To assess whether angiotensin II (Ang II) modulates key enzymes of the cyclooxygenase (COX)-2/prostanoid pathway, including prostaglandin E synthase-1 (mPGES-1) and prostacyclin synthase (PGIS) in rat aortic adventitial fibroblasts in the presence or absence of an inflammatory stimulus [interleukin (IL)-1β]. [Methods and Results]: Fibroblasts stimulated with IL-1β (10 ng/ml, 24 h) and/or Ang II (0.1 μmol/l, 24 h) were used. IL-1β up-regulated COX-2 and mPGES-1 (protein and mRNA) and increased PGI2 and PGE2 release, without altering PGIS protein expression. Ang II did modify neither COX-2 and mPGES-1 expression nor prostanoid levels, but it induced PGIS expression. Interestingly, Ang II further enhanced IL-1β-induced COX-2 expression and PGI2 release and concomitantly reduced IL-1β-induced mPGES-1 expression. The AT1 receptor antagonist losartan prevented the effects of Ang II on IL-1β-induced COX-2 or mPGES-1 expression. IL-1β activated p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK)1/2 pathways, and coincubation with Ang II resulted in a higher and more sustained phosphorylation of both MAPK. Inhibition of either p38 MAPK (SB203580) or ERK1/2 (PD98059) reduced COX-2 and mPGES-1 expression in cells treated with IL-1β or the combination of IL-1β and Ang II. Ang II did not modify COX-2 transcriptional activity but increased COX-2 mRNA stability in IL-1β-treated cells; by contrast, it increased PGIS mRNA levels through a transcriptional mechanism. [Conclusion]: Ang II differentially modulates key enzymes involved in prostanoid biosynthesis thereby altering the balance between PGI2/PGE2 in vascular cells exposed to inflammatory stimuli. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.|
|Aparece en las colecciones: ||(CIAL) Artículos|
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