Activation of thromboxane receptor upregulates interleukin (IL)-1beta-induced VCAM-1 expression through JNK signaling.
Arterioscler Thromb Vasc Biol
; 28(1): 127-34, 2008 Jan.
Article
in En
| MEDLINE
| ID: mdl-18032781
ABSTRACT
OBJECTIVE:
Activation of thromboxane receptors (TPr) is implicated in atherosclerosis and inflammation. This study examined how activation of TPr modulates IL-1beta-induced vascular cell adhesion molecule (VCAM)-1 expression in aortic vascular smooth muscle cells (VSMCs). METHODS ANDRESULTS:
In VSMCs, activation of TPr with U46619, a stable thromboxane A2 mimetic, alone did not induce VCAM-1 expression, but enhanced that caused by IL-1beta. The enhancement of VCAM-1 expression caused by U46619 occurred at the transcriptional level and was inhibited either by SP600125, a c-Jun N-terminal kinase (JNK) inhibitor, or by overexpression of a dominant-negative JNK1, but not by SB203580, a p38 mitogen-activated protein kinase inhibitor. The activation of JNK by U46619 resulted in enhanced phosphorylation and nuclear translocation of c-Jun associated with an enhanced activation of activator protein (AP)-1, which were abolished by SQ29548, a TPr antagonist, or the JNK inhibitor. Treatment of the cells with U46619 alone did not induce NF-kappaB activation. Furthermore, U46619 enhanced IL-1beta-induced THP-1 monocyte binding to VSMCs, which was inhibited by SQ29548 or SP600125.CONCLUSIONS:
This study demonstrates that activation of TPr upregulates IL-1beta-induced VCAM-1 expression by enhancing the activation of JNK pathway that leads to enhanced AP-1 activation.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aorta, Thoracic
/
Signal Transduction
/
Receptors, Thromboxane
/
Vascular Cell Adhesion Molecule-1
/
Muscle Cells
/
Interleukin-1beta
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Arterioscler Thromb Vasc Biol
Journal subject:
ANGIOLOGIA
Year:
2008
Type:
Article
Affiliation country:
United States