title: Interleukin 6 stimulates endothelial binding and transport of high-density lipoprotein through induction of endothelial lipase.
abstract: OBJECTIVE
  In the reverse cholesterol transport pathway, high-density lipoprotein (HDL) passes the endothelial cell barrier by mechanisms involving the scavenger receptor class B type I and the ATP-binding cassette G1. However, little is known on how inflammation influences this transendothelial transport.
  
  
  RESULTS
  On stimulation with interleukin-6, cultivated primary endothelial cells showed increased binding and transport of (125)I-HDL without changing the expression of scavenger receptor class B type I and ATP-binding cassette G1. Therefore, we analyzed the involvement of endothelial lipase (EL), a known HDL-binding protein expressed by endothelial cells. Here, we show an increased EL expression after interleukin-6 stimulation. Moreover, using pharmacological inhibitors or RNA interference against EL, we demonstrated its participation in HDL binding and transport through the endothelium. Furthermore, adenovirus-mediated transfection of endothelial cells with either catalytically active or nonactive EL revealed that EL facilitates the endothelial binding and transport by both bridging and lipolysis of HDL. EL was also found responsible for the reduction of HDL particle size occurring during the specific transport through a monolayer of endothelial cells. Finally, pharmacological inhibition of EL reversed the inducing effect of interleukin-6 on HDL binding and transport.
  
  
  CONCLUSIONS
  Interleukin-6 stimulates the translocation of HDL through the endothelium, the first step in reverse cholesterol transport pathway, by enhancing EL expression. In addition, we demonstrated the role of EL in the transendothelial transport of HDL.
authors.affiliation: From the Institute of Clinical Chemistry, University Hospital of Zurich, Zurich, Switzerland (J.R., M.L., D.P., A.v.E., L.R.); Zurich Center of Integrated Human Physiology, University of Zurich, Zurich, Switzerland (J.R., D.P., A.v.E., L.R.); and Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University Graz, Graz, Austria (S.F.).
authors.forename: Jérôme
authors.initials: J
authors.lastname: Robert
authors.forename: Marc
authors.initials: M
authors.lastname: Lehner
authors.forename: Saša
authors.initials: S
authors.lastname: Frank
authors.forename: Damir
authors.initials: D
authors.lastname: Perisa
authors.forename: Arnold
authors.initials: A
authors.lastname: von Eckardstein
authors.forename: Lucia
authors.initials: L
authors.lastname: Rohrer
mesh_terms: D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005822:Genetic Vectors; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008049:Lipase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008075:Lipoproteins, HDL / Q000378:metabolism*; D010316:Particle Size; D034622:RNA Interference; D051122:Scavenger Receptors, Class B / Q000378:metabolism; D014162:Transfection
chemical_list: C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D015850:Interleukin-6; D008075:Lipoproteins, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; C410382:LIPG protein, human; D008049:Lipase
keywords: cholesterol; endothelial cells; endothelial lipase, human; high-density lipoprotein; inflammation; interleukin-6