Transcriptional potencies of inhaled glucocorticoids

Am J Respir Crit Care Med. 2000 Jul;162(1):57-63. doi: 10.1164/ajrccm.162.1.9901006.


Glucocorticoids (GC) are the most effective anti-inflammatory drugs used in asthma. By a process called trans-activation, they increase the transcription of genes involved in either beneficial processes or certain side effects. Through trans-repression, they inhibit the transcription factors nuclear factor kappa B (NF-kappaB) and activator protein-1 (AP-1), thereby decreasing the expression of many genes encoding inflammatory mediators such as the cytokine RANTES. We have measured the trans-activation and trans-repression potencies of the five currently available inhaled GC using reporter gene assays. The rank order of trans-activation potencies in HeLa cells stably transfected with a GC-inducible luciferase gene was fluticasone propionate > budesonide and triamcinolone acetonide > beclomethasone dipropionate and flunisolide. For all GC except beclomethasone dipropionate, there was a highly significant correlation between their potency to trans-activate in HeLa cells and their capacity to induce the gluconeogenic enzyme tyrosine aminotransferase in hepatoma tissue culture (HTC) cells. The rank order of trans-repression potencies in A549 lung cells transiently transfected with an AP-1- or NF-kappaB-dependent luciferase gene was fluticasone propionate > budesonide > beclomethasone dipropionate, triamcinolone acetonide, and flunisolide. The same rank order was found for inhibition of RANTES release. Thus, determination of trans-repression and trans-activation potencies of GC may help to predict their capacity to produce anti-inflammatory and side effects, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Cells, Cultured
  • Chemokine CCL5 / genetics
  • Genes, tat / drug effects
  • Genes, tat / genetics
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / pharmacology*
  • Humans
  • NF-kappa B / drug effects
  • NF-kappa B / genetics
  • Transcription Factor AP-1 / drug effects
  • Transcription Factor AP-1 / genetics
  • Transcription, Genetic / drug effects*
  • Transcriptional Activation / drug effects*


  • Chemokine CCL5
  • Glucocorticoids
  • NF-kappa B
  • Transcription Factor AP-1