Inhibition of VCAM-1 expression in human bronchial epithelial cells by glucocorticoids

Am J Respir Cell Mol Biol. 1999 Apr;20(4):643-50. doi: 10.1165/ajrcmb.20.4.3265.


We have demonstrated previously that cytokines induce surface expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on BEAS-2B bronchial epithelial cells in vitro. The present studies demonstrate glucocorticoid inhibition of cytokine-induced VCAM-1 expression as detected using flow cytometry and Northern blot analysis. Several commonly used inhaled glucocorticoids were tested for their ability to inhibit VCAM-1 and ICAM-1 expression. All glucocorticoids tested inhibited VCAM-1 expression in a dose-dependent manner. No inhibition of ICAM-1 expression was observed. The most potent of the glucocorticoids tested for inhibition of VCAM-1 expression were mometasone furoate and fluticasone propionate (FP), which had IC50 values (i.e., concentrations at which each glucocorticoid produced 50% inhibition) of under 10 pM. Budesonide, triamcinolone acetonide, and beclomethasone dipropionate (BDP) had intermediate potency, and hydrocortisone and the BDP metabolite beclomethasone-17-monopropionate were the least potent of the steroids tested. Kinetic analysis of the ability of FP to inhibit VCAM-1 expression revealed that preincubation with FP for 3 h completely inhibited VCAM-1 expression induced by tumor necrosis factor-alpha (TNF-alpha). FP inhibited VCAM-1 expression by 50% even when added as late as 6 h after stimulation with TNF-alpha. Using Northern blot analysis, we confirmed inhibition of VCAM-1 and ICAM-1 messenger RNA (mRNA) expression by FP. Pretreatment with FP (10(-11) M to about 10(-7) M, 24 h) inhibited TNF-alpha-induced VCAM-1 mRNA expression in BEAS-2B in a dose-dependent manner, but did not inhibit expression of ICAM-1 mRNA. Studies with actinomycin D indicate that FP treatment accelerated the degradation of TNF-alpha-induced VCAM-1 mRNA. FP (10(-7) M) also inhibited VCAM-1 mRNA expression induced by TNF-alpha in primary human bronchial epithelial cells as assessed by reverse transcription-polymerase chain reaction. These results suggest that suppression of epithelial VCAM-1 expression by glucocorticoids may contribute to their anti-inflammatory effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Anti-Inflammatory Agents / pharmacology
  • Beclomethasone / pharmacology
  • Bronchi / cytology
  • Bronchi / drug effects
  • Bronchi / immunology*
  • Cell Line
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology*
  • Fluticasone
  • Gene Expression Regulation / drug effects*
  • Glucocorticoids / pharmacology*
  • Humans
  • Hydrocortisone / pharmacology
  • Kinetics
  • Mometasone Furoate
  • Pregnadienediols / pharmacology
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic / drug effects*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Cell Adhesion Molecule-1 / genetics*


  • Androstadienes
  • Anti-Inflammatory Agents
  • Glucocorticoids
  • Pregnadienediols
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Mometasone Furoate
  • Fluticasone
  • Beclomethasone
  • Hydrocortisone