title: TLR4-mediated inflammatory activation of human coronary artery endothelial cells by LPS.
abstract: OBJECTIVE
  Blood levels of cytokines are commonly elevated in severe congestive heart failure (CHF) and in coronary artery disease (CAD). While the adverse effects of cytokines on contractile function and myocardial cell integrity are well studied, little is known on whether cardiac cells are only targets or active players in these inflammatory reactions.
  
  
  RESULTS
  We tested if human coronary artery endothelial cells (HCAEC) may become a source of cytokine and adhesion molecule expression when stimulated with bacterial lipopolysaccharide (LPS). Analysis of HCAEC supernatants by ELISA identified enhanced secretion of IL-6, IL-8, and MCP-1 while endothelin-1 was not increased. IL-1beta, IL-10, or TNF-alpha were not detectable by ELISA while RT-PCR revealed enhanced mRNA expression of IL-1beta and TNF-alpha but not IL-10. FACS analysis showed an LPS-induced upregulation of ICAM-1, VCAM, and ELAM-1. LFA-1 could not be detected. We further characterized receptors involved in LPS-induced signaling. Our results indicate that activation of HCAEC by LPS requires Toll-like receptor (TLR) 4. Pretreating the cells with the 3-hydroxy-3-methylglutaryl CoA (HMG CoA) reductase inhibitor Cerivastatin reduced IL-6 release.
  
  
  CONCLUSIONS
  Taken together, our results indicate that activated HCAEC may act as inflammatory cells and thus directly contribute to the progression of CHF and CAD.
authors.affiliation: Department of Medicine II, Medical University of Luebeck, Ratzeburger Allee 160, Luebeck, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Zeuke
authors.forename: Artur J
authors.initials: AJ
authors.lastname: Ulmer
authors.forename: Shoichi
authors.initials: S
authors.lastname: Kusumoto
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.forename: Holger
authors.initials: H
authors.lastname: Heine
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D003331:Coronary Vessels; D016207:Cytokines / Q000378:metabolism*; D029721:Drosophila Proteins; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000276:immunology*; D006017:Glycolipids; D006333:Heart Failure / Q000276:immunology / Q000382:microbiology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008050:Lipid A / Q000031:analogs & derivatives*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013268:Stimulation, Chemical; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D016207:Cytokines; D029721:Drosophila Proteins; D019040:E-Selectin; D006017:Glycolipids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D008050:Lipid A; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011725:Pyridines; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C040142:lipid A precursors, bacterial; D018799:Intercellular Adhesion Molecule-1; C086276:cerivastatin