Protective effects of propofol on lipopolysaccharide-activated endothelial cell barrier dysfunction.
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.
Gao
J
J
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
Zhao
W X
WX
Zhou
L J
LJ
Zeng
B X
BX
Yao
S L
SL
Liu
D
D
Chen
Z Q
ZQ
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
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