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Does TNF-alpha directly increase endothelial cell monolayer permeability?
1Children's Research Centre, Our Lady's Hospital for Sick Children, Dublin, Ireland.
Agents and Actions
|January 1, 1993
Summary
Dexamethasone (DEX) blocks tumor necrosis factor-alpha (TNF-alpha)-induced increases in human umbilical vein endothelial cell permeability. While DEX shows effects, N omega-nitro-L-arginine methyl ester (L-NAME) does not, suggesting complex mechanisms beyond nitric oxide inhibition.
Area of Science:
- Endocrinology
- Cell Biology
- Immunology
Background:
- Endothelial cell permeability is crucial for regulating substance exchange.
- Tumor necrosis factor-alpha (TNF-alpha) is a key inflammatory cytokine that increases endothelial permeability.
- Dexamethasone (DEX) is a potent anti-inflammatory corticosteroid, and N omega-nitro-L-arginine methyl ester (L-NAME) is a nitric oxide synthase inhibitor.
Purpose of the Study:
- To investigate the effects of DEX and L-NAME on TNF-alpha-induced endothelial cell permeability.
- To elucidate the role of nitric oxide (NO) in mediating TNF-alpha-induced permeability changes.
Main Methods:
- Human umbilical vein endothelial cell (HUVEC) monolayers were used.
- Cells were treated with TNF-alpha, DEX, and L-NAME.
- Permeability was assessed by measuring [125I] labelled bovine serum albumin (BSA) passage.
Main Results:
- Preincubation with DEX completely abolished TNF-alpha's effect on permeability.
- DEX administered after TNF-alpha also reduced permeability.
- L-NAME showed no significant effect on TNF-alpha-induced permeability.
Conclusions:
- DEX effectively inhibits TNF-alpha-induced endothelial permeability.
- The results suggest NO may play a role, but L-NAME experiments do not fully confirm this.
- DEX might act through mechanisms beyond NO synthase inhibition, especially when administered post-TNF-alpha.