title: Preconditioning of carbon monoxide releasing molecule-derived CO attenuates LPS-induced activation of HUVEC.
abstract: OBJECTIVE
  To investigate the effects and potential mechanisms of preconditioning of tricarbonyldichlororuthenium (III) dimer (CORM-2)-liberated CO on LPS-induced activation of endothelial cells (HUVEC).
  
  
  METHODS
  HUVEC were pretreated with CORM-2 at the concentration of 50 or 100 microM for 2 hrs, washed and stimulated with LPS (10 microg/ml) for additional 4 hrs. Activation (oxidative stress) of HUVEC was assessed by measuring intracellular oxidation of DHR 123 or nitration of DAF-FM, specific H(2)O(2) and NO fluorochromes, respectively. The expression of HO-1, iNOS (Western blot) and ICAM-1 (cell ELISA) proteins and activation of inflammation-relevant transcription factor, NF-kappaB (EMSA) were assessed. In addition, PMN adhesion to HUVEC was also assessed.
  
  
  RESULTS
  The obtained data indicate that pretreatment of HUVEC with CORM-2 results in: 1) decrease of LPS-induced production of ROS and NO; 2) up-regulation of HO-1 but decrease in iNOS at the protein levels; 3) inhibition of LPS-induced activation of NF-kappaB; and 4) downregulation of expression of ICAM-1, and this was accompanied by a decrease of PMN adhesion to LPS-stimulated HUVEC.
  
  
  CONCLUSIONS
  Preconditioning of CO liberated by CORM-2 elicited its anti-inflammatory effects by interfering with the induction of intracellular oxidative stress. In addition, it also supports the notion that CO is a potent inhibitor of iNOS and NF-kappaB.
authors: Department of Burn and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, Jiangsu Province, PR China. sunbinwe@vip.sina.com
authors: Bingwei
authors: B
authors: Sun
authors: Xiangqian
authors: X
authors: Zou
authors: Yueling
authors: Y
authors: Chen
authors: Ping
authors: P
authors: Zhang
authors: Gengsheng
authors: G
authors: Shi
mesh_terms: D015153:Blotting, Western; D002248:Carbon Monoxide / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D024202:Electrophoretic Mobility Shift Assay; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009942:Organometallic Compounds / Q000378:metabolism / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D008070:Lipopolysaccharides; D009942:Organometallic Compounds; C447082:tricarbonyldichlororuthenium (II) dimer; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D002248:Carbon Monoxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D006419:Heme Oxygenase (Decyclizing)