Intermitted pharmacologic pretreatment by xenon, isoflurane, nitrous oxide, and the opioid morphine prevents tumor necrosis factor alpha-induced adhesion molecule expression in human umbilical vein endothelial cells.
BACKGROUND
The barrier properties of the endothelium are of critical importance during pathophysiologic processes. These barrier properties depend on an intact cytoskeleton and are regulated by cell adhesion molecules. Tumor necrosis factor alpha (TNF-alpha) is known to induce cell adhesion molecule expression. In myocardium, the protective effect by xenon and isoflurane preconditioning was found to be linked to the cytoskeleton. The authors investigated the impact of different anesthetics and morphine on TNF-alpha-induced endothelial cell adhesion molecule expression.


METHODS
Human umbilical vein endothelial cells were isolated from three different preparations. Cells were either left untreated or pretreated with xenon, nitrous oxide, isoflurane (each 0.43 minimum alveolar concentration), or morphine (100 ng/ml) and stimulated with 10 ng/ml TNF-alpha. Reverse-transcription polymerase chain reaction and fluorescence-activated cell sorting of intracellular cell adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin were performed. Transcriptional activity of nuclear factor kappaB was assessed by infrared electrophoretic mobility shift assay.


RESULTS
Tumor necrosis factor alpha significantly induced messenger RNA (mRNA) and protein expression of cell adhesion molecules as well as transcriptional activity of nuclear factor kappaB. All four agents prevented TNF-alpha-induced mRNA and protein expression of intracellular cell adhesion molecule 1. Vascular cell adhesion molecule 1 expression was only blocked by the inhalational anesthetics and not by morphine. None of the four agents had an effect on TNF-alpha induced E-selectin expression. TNF-alpha-induced transcriptional activity of nuclear factor kappaB was decreased by all four agents.


CONCLUSIONS
These results suggest a protective effect of anesthetics on TNF-alpha-induced endothelial cell damage.
Weber
Nina C
NC
Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Kandler
Jennis
J
Schlack
Wolfgang
W
Grueber
Yvonne
Y
Frädorf
Jan
J
Preckel
Benedikt
B
D015815:Cell Adhesion Molecules / Q000235:genetics*; D002478:Cells, Cultured; D019040:E-Selectin / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D007530:Isoflurane / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology*; D009609:Nitrous Oxide / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*; D014978:Xenon / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D014978:Xenon; D009020:Morphine; D007530:Isoflurane; D009609:Nitrous Oxide