NITRIC-OXIDE PRODUCTION AND MDR EXPRESSION BY HUMAN BRAIN ENDOTHELIAL-CELLS

The endothelium both initiates and responds to a cascade of events tri ggered by cytokines. Enhanced formation of NO, especially by inducible nitric oxide- synthase (i NOS), is largely stimulated by tumor necros is factor (TNF). Nitrogen oxides are reactive intermediate molecules f unctioning 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 i n vitro. The effect of the same agent was investigated on the MDR expr ession of endothelial cells. Both TNF and Staphylococcus aureus result ed in enhanced NO production. Western blot analysis showed enhanced ex pression of iNOS, which could be inhibited by pentoxifylline, an inhib itor of TNF synthesis. Flow cytometric analysis revealed that the brai n 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 t ools for the investigation of the possible connection between the NO p roduction and MDR function, and for the estimation the effect of diffe rent agents influencing these activities, which might be important in blood-brain barrier function.