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Angiotensin II differentially modulates cyclooxygenase-2, microsomal prostaglandin E2 synthase-1 and prostaglandin I2 synthase expression in adventitial fibroblasts exposed to inflammatory stimuli.
- Source :
-
Journal of hypertension [J Hypertens] 2011 Mar; Vol. 29 (3), pp. 529-36. - Publication Year :
- 2011
-
Abstract
- 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].<br />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.<br />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.
- Subjects :
- Animals
Aorta cytology
Aorta drug effects
Aorta enzymology
Connective Tissue enzymology
Extracellular Signal-Regulated MAP Kinases physiology
Fibroblasts enzymology
Male
Prostaglandin-E Synthases
RNA Stability
Rats
Rats, Sprague-Dawley
p38 Mitogen-Activated Protein Kinases physiology
Angiotensin II pharmacology
Connective Tissue drug effects
Cyclooxygenase 2 genetics
Cytochrome P-450 Enzyme System genetics
Fibroblasts drug effects
Interleukin-1beta pharmacology
Intramolecular Oxidoreductases genetics
Prostaglandin-Endoperoxide Synthases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1473-5598
- Volume :
- 29
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of hypertension
- Publication Type :
- Academic Journal
- Accession number :
- 21169864
- Full Text :
- https://doi.org/10.1097/HJH.0b013e328342b271