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.
From: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan.
The Journal of biological chemistry
- Publish Date: Dec 2006
- ISSN: 0021-9258
- Volume: 281
- Issue: 49
- Pages: 37457-67
- Medium: Print
- Language: English
- Citation (JAMA): Kimura Takao, Tomura Hideaki, Mogi Chihiro, et al. 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.. J. Biol. Chem. Dec 2006;281:37457-67
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).
Mesh Headings (Keywords): Cell Adhesion Molecules, Cells, Cultured, Endothelial Cells, Enzyme Activation, Humans, Intercellular Adhesion Molecule-1, Lipoproteins, HDL, Models, Biological, Nitric Oxide Synthase Type III, Receptors, Lysosphingolipid, Scavenger Receptors, Class B, Signal Transduction, Vascular Cell Adhesion Molecule-1
Check for Full Text / PubMed Unique Identifier (PMID): 17046831
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