title: In vitro effects of cyclosporin A on the expression of adhesion molecules on human umbilical vein endothelial cells.
abstract: BACKGROUND
  Among the different factors playing crucial roles in endothelial cell activation, cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) have been reported to demonstrate profound effects on this cell type. It has been shown that the increased release of IFN-alpha/gamma and TNF-alpha causes structural and functional modulations of the endothelial cell. These cytokines participate in the recruitment and activation of the immune system. CsA is an immunosuppressive drug that is necessary at high levels in human recipients of vascularised xenografts. This drug could contribute to a prolonged graft survival by modulation of endothelial cell activation.
  
  
  METHODS
  The present study deals with the effects of cyclosporin A on adhesion molecule expression (i.e. ICAM-1, VCAM-1, E-selectin, P-selectin, PECAM-1 and the L-selectin ligand CD 34) on the surface of cytokine stimulated HUVECs. The in vitro model described herein mimics the stimulation of endothelial cells by cytokines as seen during inflammatory processes after transplantation. Therefore, HUVECs were activated either with TNF-alpha, IL-1beta or with a cytokine mixture consisting of those stimulants present at an elevated level in sera of patients during allograft rejection (i.e. IL-1beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha and IFN-gamma).
  
  
  RESULTS
  The results obtained show that the immunosuppression of CsA is not only achieved by inhibiting lymphocyte proliferation, but also by decreasing the expression of adhesion molecules on endothelial cells, which are the first target of the cellular rejection process.
  
  
  CONCLUSIONS
  Co-incubation of stimulated endothelial cells with a final CsA concentration of 5 microg/ml revealed a significant down-regulating influence on the surface expression of E-selectin and VCAM-1.
authors.affiliation: Institute of Laboratory Diagnostics and Ludwig Boltzmann Institute for Cardiothoracic Research, Kaiser Franz Josef Hospital, Kundratstrasse 3, A-1100 Vienna, Austria.
authors.forename: Snezana
authors.initials: S
authors.lastname: Markovic
authors.forename: Markus
authors.initials: M
authors.lastname: Raab
authors.forename: Heide
authors.initials: H
authors.lastname: Daxecker
authors.forename: Andrea
authors.initials: A
authors.lastname: Griesmacher
authors.forename: Alireza
authors.initials: A
authors.lastname: Karimi
authors.forename: Mathias M
authors.initials: MM
authors.lastname: Müller
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000187:drug effects* / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology; D019040:E-Selectin / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007165:Immunosuppression Therapy; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D016572:Cyclosporine