Dexamethasone Inhibits Cytokine-Induced Intercellular Adhesion molecule-1 Up-Regulation on Endothelial Cell Lines

Eur J Pharmacol. 1997 Jul 16;331(1):65-71. doi: 10.1016/s0014-2999(97)01015-7.


Intercellular adhesion molecule-1 (ICAM-1) expression on three endothelial cell lines was differently modulated by pro-inflammatory cytokines, such as interleukin-1beta and tumour necrosis factor-alpha (TNF-alpha) and the glucocorticoid hormone dexamethasone. Incubation of EA.hy926 cells with 1 microM dexamethasone prior to addition of TNF-alpha consistently reduced ICAM-1 induction by approximately 40%. EA.hy926 cell responsiveness to the steroid was validated by detecting specific dexamethasone binding, with a calculated affinity constant of 1.3 nM and a maximal number of sites of 35 x 10(3) per cell. To establish the generality of dexamethasone inhibition upon ICAM-1 up-regulation, two other endothelial cell lines were assessed. Incubation of LT4 and ECV304 cells with interleukin-1beta or TNF-alpha produced a significant increase in ICAM-1 expression on their cell surface (ranging from a 2-fold increase for interleukin-1beta to a 5-fold increase for TNF-alpha). Addition of dexamethasone was again able to significantly reduced this induction. Finally, the effect of the steroid on cytokine-induced ICAM-1 up-regulation was functionally related to its ability to suppress in vitro neutrophil trans-endothelial passage. Overall these data indicate that ICAM-1 is a likely molecular target for the anti-inflammatory action exerted by dexamethasone. Inhibition of ICAM-1 up-regulation may, at least in part, mediate the potent anti-migratory action displayed by this class of anti-inflammatory drugs.

Publication types

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

MeSH terms

  • Cell Line
  • Dexamethasone / pharmacology*
  • Endothelium, Vascular / drug effects*
  • Flow Cytometry
  • Humans
  • Intercellular Adhesion Molecule-1 / biosynthesis*
  • Neutrophils
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • Dexamethasone