title: Protective effects of propofol on lipopolysaccharide-activated endothelial cell barrier dysfunction.
abstract: BACKGROUND
  Propofol has been widely used in intravenous anesthesia. It possesses antioxidant and immunomodulating effects. This study aimed to investigate whether propofol may attenuate lipopolysaccharide (LPS)-induced endothelial cell barrier dysfunction and the possible mechanisms of such modulation.
  
  
  METHODS
  Cultured human umbilical vein endothelial cells (HUVECs) were used to assess the following treatments: (i) no additives (negative control), (ii) LPS alone (1 and 10 microg/ml), (iii) propofol alone (20 microg/ml), (iv) intralipid (a solvent of propofol) alone (20 microg/ml), (v) LPS (10 microg/ml) combination with propofol (4 and 20 microg/ml) and (vi) LPS (10 microg/ml) combination with intralipid (20 microg/ml). Changes of cell permeability and filamentous actin (F-actin) were determined. Expression of nitrotyrosine proteins and activity of nuclear factor kappaB (NF-kappaB) were analyzed by Western blot and immunocytochemistry. Expression of endothelial nitric-oxide synthase (eNOS) and inducible nitric-oxide synthase (iNOS) were analyzed by reverse transcriptase-polymerase chain reaction.
  
  
  RESULTS
  LPS markedly increased the permeability of endothelial cells, the formation of peroxynitrite and depolymerization of F-actin in HUVECs. LPS also significantly increased mRNA of iNOS, protein level of NF-kappaB and decreased mRNA of eNOS (P < 0.05). Propofol at both concentrations (4 and 20 microg/ml) significantly inhibited the LPS-induced increase in cell permeability and alteration in F-actin organization. Propofol also reduced the LPS-enhanced iNOS mRNA and NF-kappaB protein levels whilst it increased eNOS mRNA expression (P < 0.05).
  
  
  CONCLUSIONS
  This study demonstrated that propofol, both at therapeutic concentrations and 5 times therapeutic concentrations, inhibited NF-kappaB activation in LPS-stimulated endothelial cells and was found to protect endothelial cells against LPS-induced barrier dysfunction.
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Guangzhou, University of Traditional Chinese Medicine, 111 Da De Road, Guangzhou 510120, Guangdong, China. gaoju_003@163.com
authors.forename: J
authors.initials: J
authors.lastname: Gao
authors.forename: W X
authors.initials: WX
authors.lastname: Zhao
authors.forename: L J
authors.initials: LJ
authors.lastname: Zhou
authors.forename: B X
authors.initials: BX
authors.lastname: Zeng
authors.forename: S L
authors.initials: SL
authors.lastname: Yao
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D016328:NF-kappa B / Q000032:analysis / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D000199:Actins; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D015742:Propofol