Stimulation with thromboxane A2 (TXA2) receptor agonist enhances ICAM-1, VCAM-1 or ELAM-1 expression by human vascular endothelial cells

Clin Exp Immunol. 1998 Jun;112(3):464-70. doi: 10.1046/j.1365-2249.1998.00614.x.

Abstract

A previous study reported that intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells (HUVEC) is augmented by intracellular signal transmission mainly through the protein kinase C (PKC) system stimulated by TXA2 receptors. In the present study, we show that a TXA2 receptor agonist, U46619, augments the expression of not only ICAM-1, but also vascular cell adhesion molecule-1 (VCAM-1) or endothelial leucocyte adhesion molecule-1 (ELAM-1) in HUVEC both at protein and mRNA levels. Pretreatment with SQ29,548 (a TXA2 receptor antagonist) or PKC inhibitors greatly diminished the extent of U46619-induced mRNA accumulation and surface expression of the adhesion molecules. An inhibitor of nuclear factor kappaB (NF-kappaB) activation, PDTC, diminishes U46619-induced VCAM-1 mRNA accumulation. NAC, which inhibits NF-kappaB and activation protein 1 (AP-1) binding activity, inhibits the expression of ICAM-1 or ELAM-1 at protein and mRNA levels. These findings suggest that ICAM-1 or ELAM-1 expression of HUVEC stimulated via TXA2 receptors is augmented by induction of NF-kappaB and AP-1 binding activity through the PKC system, and that VCAM-1 expression is augmented by induction of NF-kappaB binding activity.

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology*
  • Cells, Cultured
  • E-Selectin / biosynthesis*
  • E-Selectin / immunology
  • Endothelium, Vascular / immunology*
  • Endothelium, Vascular / metabolism*
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis*
  • Intercellular Adhesion Molecule-1 / immunology
  • NF-kappa B / metabolism
  • RNA, Messenger / analysis
  • Receptors, Thromboxane / agonists*
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Vascular Cell Adhesion Molecule-1 / biosynthesis*
  • Vascular Cell Adhesion Molecule-1 / immunology
  • Vasoconstrictor Agents / pharmacology*

Substances

  • E-Selectin
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Thromboxane
  • Vascular Cell Adhesion Molecule-1
  • Vasoconstrictor Agents
  • Intercellular Adhesion Molecule-1
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid