Nitric oxide mediates tumor necrosis factor-alpha cytotoxicity in endothelial cells

Biochem Biophys Res Commun. 1992 Jul 15;186(1):475-82. doi: 10.1016/s0006-291x(05)80832-0.


Tumor necrosis factor alpha (TNF-alpha) exerts multiple actions on endothelial cells including among others the expression of pro-coagulant activity and adhesion molecules, and secretion of cytokines. We now show that TNF-alpha induces a time- and dose-dependent cytotoxic effect on cultured bovine aortic endothelial cells. This TNF-induced cytotoxicity, which is preceded by increased production of nitric oxide (NO), is significantly decreased by the NO synthase inhibitor N-iminoethyl-L-ornithine (L-NIO). Dexamethasone, which prevents the expression of cytokine-induced NO synthase in endothelial cells, also inhibits TNF-alpha-dependent cytotoxicity. The results indicate that NO is involved in the cytotoxic effect of TNF-alpha on endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors
  • Amino Acid Oxidoreductases / metabolism*
  • Animals
  • Aorta
  • Cattle
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dexamethasone / pharmacology
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Kinetics
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase
  • Ornithine / analogs & derivatives*
  • Ornithine / pharmacology
  • Recombinant Proteins / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • N(G)-iminoethylornithine
  • Dexamethasone
  • Ornithine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases