title: Globular adiponectin induces adhesion molecule expression through the sphingosine kinase pathway in vascular endothelial cells.
abstract: The signaling pathways that couple adiponectin receptors to functional, particularly inflammatory, responses have remained elusive. We report here that globular adiponectin induces endothelial cell activation, as measured by the expression of adhesion proteins such as vascular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), E-selectin and MCP-1, through the sphingosine kinase (SKase) signaling pathway. Treatment of human umbilical vein endothelial cells with globular adiponectin resulted in NF-kappaB activation and increased mRNA levels of VCAM-1, ICAM-1, E-selectin and MCP-1. Sphingosine 1-phosphate (S1P), but not ceramide or sphingosine, was a potent stimulator of adhesion protein expression. As S1P is generated from sphingosine by SKase, we treated cells with siRNA for SKase to silence the effects of S1P in the endothelial cells. Treatment with SKase siRNA inhibited globular adiponectin-induced NF-kappaB activation and markedly decreased the globular adiponectin-induced mRNA levels of adhesion protein. Thus, we demonstrated that the SKase pathway, through the generation of S1P, is critically involved in mediating globular adiponectin-induced endothelial cell activation.
authors.affiliation: Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kase
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hattori
authors.forename: Teruo
authors.initials: T
authors.lastname: Jojima
authors.forename: Toshie
authors.initials: T
authors.lastname: Okayasu
authors.forename: Atsuko
authors.initials: A
authors.lastname: Tomizawa
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Banba
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Monden
authors.forename: Hiroko
authors.initials: H
authors.lastname: Satoh
authors.forename: Kazumi
authors.initials: K
authors.lastname: Akimoto
authors.forename: Kikuo
authors.initials: K
authors.lastname: Kasai
mesh_terms: D052242:Adiponectin / Q000378:metabolism / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D018932:Chemokine CCL2 / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D015398:Signal Transduction; D014471:Umbilical Veins / Q000166:cytology; D000099157:Sphingosine Kinase