Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 52, Issue 9, Pages 1760-1766Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2012.02.052
Keywords
Interleukin; Monocyte adhesion; NADPH oxidase; Nitric oxide; Thromboxane receptor
Funding
- American Heart Association [09GRNT210017]
- National Institute of Health [R01 HL083358, R01 AG27080, R01 HL105287]
- Vascular Biology Section at Boston University Medical Center
- Institut de Recherche Servier
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Activation of thromboxane receptors (TPr) may promote atherosclerosis by enhancing oxidative stress and inflammation. This study examined the role of Nox1, an NADPH-oxidase subunit, in the enhancement of interleukin (IL)-1 beta-induced monocyte adhesion by TPr. In cultured rat aortic vascular smooth muscle cells (VSMCs), U46619, a stable thromboxane A(2) mimetic, together with interleukin-1 beta significantly enhanced Nox1 mRNA expression, as well as adhesion of THP-1 monocytes. Activation of TPr also enhanced induced vascular cell adhesion molecule (VCAM)-1 expression, but inhibited inducible nitric oxide synthase (iNOS) expression. Silencing Nox1 expression by siRNA prevented the U46619 enhancement of IL-1 beta-induced monocyte adhesion, but had no significant effect on VCAM-1 or iNOS expression. Furthermore, monocyte adhesion was inhibited by superoxide dismutase, enhanced by a specific iNOS inhibitor, t-N-6-(1-iminoethyl)-lysine, but not influenced by catalase. U46619 inhibited IL-1 beta-induced cyclic GMP production, and the inhibition was partially prevented by superoxide dismutase. In conclusion, activation of TPr enhances IL-1 beta-induced Nox1 expression in VSMCs, which is responsible for the up-regulation of monocyte adhesion. The effect of Nox1 is independent of the changes in VCAM-1 and iNOS expression, but depends on the inactivation of nitric oxide via generation of superoxide anion. (c) 2012 Elsevier Inc. All rights reserved.
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