Increase in surface expression of ICAM-1, VCAM-1 and E-selectin in human cerebromicrovascular endothelial cells subjected to ischemia-like insults

Acta Neurochir Suppl. 1997;70:12-6. doi: 10.1007/978-3-7091-6837-0_4.

Abstract

Secondary ischemic brain injury has been shown to develop as a consequence of inflammation and vasogenic brain edema. In this study we show that inflammatory cytokines and simulated in vitro ischemia stimulate the surface expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial-leukocyte adhesion molecule-1 (E-selectin) in human cerebromicrovascular endothelial cells (HCEC) in culture. The levels of all three adhesion molecules were dramatically (3 to 10-fold) up-regulated by 4-24 hour exposure to the inflammatory cytokines. IL-1 beta (10-200 u/ml) or TNF alpha (50 200 u/ml), and by a 4 hour exposure to "simulated" in vitro ischemia, as determined by immunocytochemistry and ELISA. Following 24 hours of subsequent reperfusion, the expression of ICAM-1 and VCAM-1 was maintained at ischemia-induced levels, whereas E-selectin was no longer detectable. Both the cytokine- and ischemia-induced up-regulation of adhesion molecules were completely abolished by the transcriptional inhibitor, actinomycin D (10 micrograms/ml), and inhibited by the cycloxygenase (COX) inhibitor, indomethacin (300 microM). These findings implicate HCEC in the processes of leukocyte adhesion and recruitment in the brain during stroke in vivo.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • Cell Line
  • Cytokines / pharmacology
  • E-Selectin / biosynthesis*
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / pathology
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis*
  • Models, Biological
  • Transcription, Genetic
  • Vascular Cell Adhesion Molecule-1 / biosynthesis*

Substances

  • Cytokines
  • E-Selectin
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1