Back to Search
Start Over
Urocortin induced expression of COX-2 and ICAM-1 via corticotrophin-releasing factor type 2 receptor in rat aortic endothelial cells.
- Source :
- British Journal of Pharmacology; Oct2009, Vol. 158 Issue 3, p819-829, 11p
- Publication Year :
- 2009
-
Abstract
- <bold>Background and Purpose: </bold>Our previous study showed that urocortin (Ucn1) exacerbates the hypercoagulable state and vasculitis in a rat model of sodium laurate-induced thromboangiitis obliterans. Furthermore, the inflammatory molecules COX-2 and ICAM-1 may participate in this effect. In the present study, the effects of Ucn1 on COX-2 and ICAM-1 expression in lipopolysaccharide (LPS)-induced rat aortic endothelial cells (RAECs) were investigated and the mechanisms involved explored.<bold>Experimental Approach: </bold>RAECs were isolated from adult male Wistar rats, and identified at the first passage. Experiments were performed on cells, from primary culture, at passages 5-8. The expression of COX-2 and ICAM-1 at both mRNA and protein levels was determined by semi-quantitative RT-PCR and Western blot analysis. Levels of PGE(2) and soluble ICAM-1 (sICAM-1) in culture medium were measured by enzyme-linked immunosorbent assay. Furthermore, the phosphorylation status of p38MAPK, ERK1/2, JNK, Akt and NF-kappaB was analysed by Western blot; nuclear translocation of NF-kappaB was observed by immunofluorescence.<bold>Key Results: </bold>Ucn1 augmented LPS-induced expression of COX-2 and ICAM-1 in RAECs in a time- and concentration-dependent manner. Ucn1 increased PGE(2) and sICAM-1 levels. These effects were abolished by the CRF(2) receptor antagonist, antisauvagine-30, but not by the CRF(1) receptor antagonist, NBI-27914. Moreover, Ucn2 activated p38MAPK and augmented NF-kappaB nuclear translocation and phosphorylation, whereas ERK1/2, JNK and Akt pathways were not involved in this process.<bold>Conclusions and Implications: </bold>These findings suggest that Ucn1 exerts pro-inflammatory effects by augmenting LPS-induced expression of COX-2 and ICAM-1 in RAECs via CRF(2) receptors and the activation of p38MAPK and NF-kappaB. [ABSTRACT FROM AUTHOR]
- Subjects :
- VASCULITIS treatment
GENE expression
CYCLOOXYGENASE 2
ADRENOCORTICOTROPIC hormone
IMMUNOFLUORESCENCE
ENZYME-linked immunosorbent assay
HORMONE receptors
LABORATORY rats
LIPOPOLYSACCHARIDES
BIOCHEMISTRY
RESEARCH
CORTICOTROPIN releasing hormone
BIOLOGICAL transport
DINOPROSTONE
HETEROCYCLIC compounds
ANIMAL experimentation
RESEARCH methodology
CELL receptors
MEDICAL cooperation
EVALUATION research
AMINES
RATS
PHENOMENOLOGY
COMPARATIVE studies
DNA-binding proteins
TRANSFERASES
AORTA
OXIDOREDUCTASES
EPITHELIAL cells
ANTIGENS
PEPTIDES
PHOSPHORYLATION
Subjects
Details
- Language :
- English
- ISSN :
- 00071188
- Volume :
- 158
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- British Journal of Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 65012701
- Full Text :
- https://doi.org/10.1111/j.1476-5381.2009.00346.x