Does TNF-α directly increase endothelial cell monolayer permeability?
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The effects of dexamethasone (DEX) and ϖ methyl ester (l-NAME) on the tumour necrosis factor-α (TNF-α)-induced increase in permeability of human umbilical vein endothelial cell (HUVEC) monolayer to [125I] labelled bovine serum albumin (BSA) were examined. Preincubation of HUVEC monolayers with DEX (1μM, 2 h) completely abolished the effect of TNF-α (5 ng/ml, 18 h). Administration of DEX 2 h after TNF-α also reduced the effect of TNF-α, whilel-NAME (5 ng/ml, 1 mM, 18 h) had no significant effect.
The observed inhibition of the TNF-α-induced permeability increase on preincubation with DEX would suggest a role for nitric oxide (NO) in mediating the permeability response. However, this is not confirmed by the experiments withl-NAME. The inhibition caused by DEX administered after TNF-α would suggest alternative mechanisms by which DEX may be acting in addition to inhibition of NO synthase induction.
KeywordsMethyl Ester Nitric Oxide Bovine Serum Albumin Tumour Necrosis
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