DOES TNF-ALPHA DIRECTLY INCREASE ENDOTHELIAL-CELL MONOLAYER PERMEABILITY

The effects of dexamethasone (DEX) and NomegaBAR-nitro-L-arginine meth yl ester (L-NAME) on the tumour necrosis factor-alpha (TNF-alpha)-indu ced increase in permeability of human umbilical vein endothelial cell (HUVEC) monolayer to [I-125] labelled bovine serum albumin (BSA) were examined. Preincubation of HUVEC monolayers with DEX (1 muM, 2 h) comp letely abolished the effect of TNF-alpha (5 ng/ml, 18 h). Administrati on of DEX 2 h after TNF-alpha also reduced the effect of TNF-alpha whi le L-NAME (5 ng/ml, 1 mM, (8 h) had no significant effect. The observe d inhibition of the TNF-alpha-induced permeability increase on preincu bation with DEX would suggest a role for nitric oxide (NO) in mediatin g the permeability response. However, this is not confirmed by the exp eriments with L-NAME. The inhibition caused by DEX administered after TNF-alpha would suggest alternative mechanisms by which DEX may be act ing in addition to inhibition of NO synthase induction.