title: Salusin-β accelerates inflammatory responses in vascular endothelial cells via NF-κB signaling in LDL receptor-deficient mice in vivo and HUVECs in vitro.
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.
authors.affiliation: Department of Biochemistry, Showa University School of Medicine, Hatanodai, Shinagawa-ku, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Koya
authors.forename: Takuro
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Takuya
authors.initials: T
authors.lastname: Watanabe
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Shichiri
authors.forename: Takashi
authors.initials: T
authors.lastname: Atsumi
authors.forename: Joo-ri
authors.initials: JR
authors.lastname: Kim-Kaneyama
authors.forename: Akira
authors.initials: A
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002791:Cholesterol, Dietary / Q000494:pharmacology; D004396:Coloring Agents; D017931:DNA Primers; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007958:Leukocyte Count; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects; D019255:NADPH Oxidases / Q000096:biosynthesis / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D011973:Receptors, LDL / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013778:Tetrazolium Salts; D013844:Thiazoles; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology; D014657:Vasculitis / Q000139:chemically induced* / Q000473:pathology*
chemical_list: D002791:Cholesterol, Dietary; D004396:Coloring Agents; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D011973:Receptors, LDL; C478739:TOR2A protein, human; D013778:Tetrazolium Salts; D013844:Thiazoles; D019010:Vascular Cell Adhesion Molecule-1; D019255:NADPH Oxidases; C022616:thiazolyl blue