title: Role of scavenger receptor class B type I and sphingosine 1-phosphate receptors in high density lipoprotein-induced inhibition of adhesion molecule expression in endothelial cells.
abstract: We characterized the molecular mechanisms by which high density lipoprotein (HDL) inhibits the expression of adhesion molecules, including vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, induced by sphingosine 1-phosphate (S1P) and tumor necrosis factor (TNF) alpha in endothelial cells. HDL inhibited S1P-induced nuclear factor kappaB activation and adhesion molecule expression in human umbilical vein endothelial cells. The inhibitory HDL actions were associated with nitric-oxide synthase (NOS) activation and were reversed by inhibitors for phosphatidylinositol 3-kinase and NOS. The HDL-induced inhibitory actions were also attenuated by the down-regulation of scavenger receptor class B type I (SR-BI) and its associated protein PDZK1. When TNFalpha was used as a stimulant, the HDL-induced NOS activation and the inhibitory action on adhesion molecule expression were, in part, attenuated by the down-regulation of the expression of S1P receptors, especially S1P(1), in addition to SR-BI. Reconstituted HDL composed mainly of apolipoprotein A-I and phosphatidylcholine mimicked the SR-BI-sensitive part of HDL-induced actions. Down-regulation of S1P(3) receptors severely suppressed the stimulatory actions of S1P. Although G(i/o) proteins may play roles in either stimulatory or inhibitory S1P actions, as judged from pertussis toxin sensitivity, the coupling of S1P(3) receptors to G(12/13) proteins may be critical to distinguish the stimulatory pathways from the inhibitory ones. In conclusion, even though S1P alone stimulates adhesion molecule expression, HDL overcomes S1P(3) receptor-mediated stimulatory actions through SR-BI/PDZK1-mediated signaling pathways involving phosphatidylinositol 3-kinase and NOS. In addition, the S1P component of HDL plays a role in the inhibition of TNFalpha-induced actions through S1P receptors, especially S1P(1).
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Kimura
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tomura
authors.forename: Chihiro
authors.initials: C
authors.lastname: Mogi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kuwabara
authors.forename: Alatangaole
authors.initials: A
authors.lastname: Damirin
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sekiguchi
authors.forename: Mitsuteru
authors.initials: M
authors.lastname: Ishiwara
authors.forename: Doon-Soon
authors.initials: DS
authors.lastname: Im
authors.forename: Koichi
authors.initials: K
authors.lastname: Sato
authors.forename: Masami
authors.initials: M
authors.lastname: Murakami
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Okajima
mesh_terms: D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism* / Q000494:pharmacology; D008954:Models, Biological; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D051122:Scavenger Receptors, Class B / Q000378:metabolism*; D015398:Signal Transduction; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D008075:Lipoproteins, HDL; D049349:Receptors, Lysosphingolipid; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III