Nitric oxide production and MDR expression by human brain endothelial cells.
The endothelium both initiates and responds to a cascade of events triggered by cytokines. Enhanced formation of NO, especially by inducible nitric oxide- synthase (i NOS), is largely stimulated by tumor necrosis factor (TNF). Nitrogen oxides are reactive intermediate molecules functioning in neural transmission, and vasodilatation. The aim of our study was to investigate the effect of TNF and Staphylococcus aureus, a TNF inducing agent on the NO production of brain endothelial cells in vitro. The effect of the same agent was investigated on the MDR expression of endothelial cells. Both TNF and Staphylococcus aureus resulted in enhanced NO production. Western blot analysis showed enhanced expression of iNOS, which could be inhibited by pentoxifylline, an inhibitor of TNF synthesis. Flow cytometric analysis revealed that the brain capillary endothelial cells exerted P-glycoprotein expression, which was not influenced by TNF. However, the mdr function itself in these cells was decreased by TNF. Cultured endothelial cells are excellent tools for the investigation of the possible connection between the NO production and MDR function, and for the estimation the effect of different agents influencing these activities, which might be important in blood-brain barrier function.
Mándi
Y
Y
Department of Microbiology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Ocsovszki
I
I
Szabo
D
D
Nagy
Z
Z
Nelson
J
J
Molnar
J
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply*; D018432:Drug Resistance, Multiple / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D013211:Staphylococcus aureus; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II