1. Salusin-β accelerates inflammatory responses in vascular endothelial cells via NF-κB signaling in LDL receptor-deficient mice in vivo and HUVECs in vitro.
- Author
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Koya T, Miyazaki T, Watanabe T, Shichiri M, Atsumi T, Kim-Kaneyama JR, and Miyazaki A
- Subjects
- Animals, Blood Pressure drug effects, Cell Adhesion drug effects, Cholesterol, Dietary pharmacology, Coloring Agents, DNA Primers, Endothelial Cells pathology, Humans, Immunohistochemistry, Leukocyte Count, Mice, Mice, Knockout, Monocytes drug effects, NADPH Oxidases biosynthesis, NADPH Oxidases physiology, Oxidative Stress drug effects, Real-Time Polymerase Chain Reaction, Receptors, LDL genetics, Tetrazolium Salts, Thiazoles, Vascular Cell Adhesion Molecule-1 physiology, Endothelial Cells drug effects, Human Umbilical Vein Endothelial Cells drug effects, Intercellular Signaling Peptides and Proteins pharmacology, NF-kappa B physiology, Receptors, LDL physiology, Signal Transduction drug effects, Vasculitis chemically induced, Vasculitis pathology
- Abstract
The bioactive peptide salusin-β is highly expressed in human atheromas; additionally, infusion of antiserum against salusin-β suppresses the development of atherosclerosis in atherogenic mice. This study examined the roles of salusin-β in vascular inflammation during atherogenesis. Infusion of antiserum against salusin-β attenuated the induction of VCAM-1, monocyte chemoattractant protein (MCP)-1, and IL-1β and as well as nuclear translocation of NF-κB in aortic endothelial cells (ECs) of LDL receptor-deficient mice, which led to the prevention of monocyte adhesion to aortic ECs. In vitro experiments indicated that salusin-β directly enhances the expression levels of proinflammatory molecules, including VCAM-1, MCP-1, IL-1β, and NADPH oxidase 2, as well as THP-1 monocyte adhesion to cultured human umbilical vein ECs (HUVECs). Both salusin-β-induced VCAM-1 induction and monocyte/HUVEC adhesion were suppressed by pharmacological inhibitors of NF-κB, e.g., Bay 11-7682 and curcumin. Furthermore, the VCAM-1 induction was significantly prevented by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002, whereas it was accelerated by the ERK inhibitor, U-0126. Treatment of HUVECs with salusin-β, but not with salusin-α, accelerated oxidative stress and nuclear translocation of NF-κB as well as phosphorylation and degradation of IκB-α, an endogenous inhibitor of NF-κB. Thus, salusin-β enhanced monocyte adhesion to vascular ECs through NF-κB-mediated inflammatory responses in ECs, which can be modified by PI3K or ERK signals. These findings are suggestive of a novel role of salusin-β in atherogenesis. more...
- Published
- 2012
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