Corticosteroid-induced gene expression in allergen-challenged asthmatic subjects taking inhaled budesonide

Br J Pharmacol. 2012 Mar;165(6):1737-1747. doi: 10.1111/j.1476-5381.2011.01620.x.


Background and purpose: Inhaled corticosteroids (ICS) are the cornerstone of asthma pharmacotherapy and, acting via the glucocorticoid receptor (GR), reduce inflammatory gene expression. While this is often attributed to a direct inhibitory effect of the GR on inflammatory gene transcription, corticosteroids also induce the expression of anti-inflammatory genes in vitro. As there are no data to support this effect in asthmatic subjects taking ICS, we have assessed whether ICS induce anti-inflammatory gene expression in subjects with atopic asthma.

Experimental approach: Bronchial biopsies from allergen-challenged atopic asthmatic subjects taking inhaled budesonide or placebo were subjected to gene expression analysis using real-time reverse transcriptase-PCR for the corticosteroid-inducible genes (official gene symbols with aliases in parentheses): TSC22D3 [glucocorticoid-induced leucine zipper (GILZ)], dual-specificity phosphatase-1 (MAPK phosphatase-1), both anti-inflammatory effectors, and FKBP5 [FK506-binding protein 51 (FKBP51)], a regulator of GR function. Cultured pulmonary epithelial and smooth muscle cells were also treated with corticosteroids before gene expression analysis.

Key results: Compared with placebo, GILZ and FKBP51 mRNA expression was significantly elevated in budesonide-treated subjects. Budesonide also increased GILZ expression in human epithelial and smooth muscle cells in culture. Immunostaining of bronchial biopsies revealed GILZ expression in the airways epithelium and smooth muscle of asthmatic subjects.

Conclusions and implications: Expression of the corticosteroid-induced genes, GILZ and FKBP51, is up-regulated in the airways of allergen-challenged asthmatic subjects taking inhaled budesonide. Consequently, the biological effects of corticosteroid-induced genes should be considered when assessing the actions of ICS. Treatment modalities that increase or decrease GR-dependent transcription may correspondingly affect corticosteroid efficacy.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / therapeutic use*
  • Allergens / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Asthma / drug therapy
  • Asthma / genetics*
  • Bronchodilator Agents / therapeutic use*
  • Budesonide / therapeutic use*
  • Cell Line, Tumor
  • Cross-Over Studies
  • Dual Specificity Phosphatase 1 / genetics
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Gene Expression / drug effects*
  • Humans
  • Lung / cytology
  • Lung / drug effects
  • Lung / metabolism
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tacrolimus Binding Proteins / genetics
  • Transcription Factors / genetics


  • Adrenal Cortex Hormones
  • Allergens
  • Anti-Inflammatory Agents
  • Bronchodilator Agents
  • RNA, Messenger
  • TSC22D3 protein, human
  • Transcription Factors
  • Budesonide
  • Dual Specificity Phosphatase 1
  • Tacrolimus Binding Proteins
  • tacrolimus binding protein 5