title: Corticosteroid-induced gene expression in allergen-challenged asthmatic subjects taking inhaled budesonide.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: Airways Inflammation Research Group, Institute of Infection, Immunity and Inflammation, Faculty of Medicine, University of Calgary, Calgary, AB, CanadaAllergy and Immunology Section, University of California, San Diego School of Medicine, La Jolla, CA, USAFirestone Institute for Respiratory Health, St. Joseph's Hospital and the Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: M M
authors.initials: MM
authors.lastname: Kelly
authors.affiliation: Airways Inflammation Research Group, Institute of Infection, Immunity and Inflammation, Faculty of Medicine, University of Calgary, Calgary, AB, CanadaAllergy and Immunology Section, University of California, San Diego School of Medicine, La Jolla, CA, USAFirestone Institute for Respiratory Health, St. Joseph's Hospital and the Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: E M
authors.initials: EM
authors.lastname: King
authors.affiliation: Airways Inflammation Research Group, Institute of Infection, Immunity and Inflammation, Faculty of Medicine, University of Calgary, Calgary, AB, CanadaAllergy and Immunology Section, University of California, San Diego School of Medicine, La Jolla, CA, USAFirestone Institute for Respiratory Health, St. Joseph's Hospital and the Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: C F
authors.initials: CF
authors.lastname: Rider
authors.affiliation: Airways Inflammation Research Group, Institute of Infection, Immunity and Inflammation, Faculty of Medicine, University of Calgary, Calgary, AB, CanadaAllergy and Immunology Section, University of California, San Diego School of Medicine, La Jolla, CA, USAFirestone Institute for Respiratory Health, St. Joseph's Hospital and the Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Gwozd
authors.affiliation: Airways Inflammation Research Group, Institute of Infection, Immunity and Inflammation, Faculty of Medicine, University of Calgary, Calgary, AB, CanadaAllergy and Immunology Section, University of California, San Diego School of Medicine, La Jolla, CA, USAFirestone Institute for Respiratory Health, St. Joseph's Hospital and the Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: N S
authors.initials: NS
authors.lastname: Holden
authors.affiliation: Airways Inflammation Research Group, Institute of Infection, Immunity and Inflammation, Faculty of Medicine, University of Calgary, Calgary, AB, CanadaAllergy and Immunology Section, University of California, San Diego School of Medicine, La Jolla, CA, USAFirestone Institute for Respiratory Health, St. Joseph's Hospital and the Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Eddleston
authors.affiliation: Airways Inflammation Research Group, Institute of Infection, Immunity and Inflammation, Faculty of Medicine, University of Calgary, Calgary, AB, CanadaAllergy and Immunology Section, University of California, San Diego School of Medicine, La Jolla, CA, USAFirestone Institute for Respiratory Health, St. Joseph's Hospital and the Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Zuraw
authors.affiliation: Airways Inflammation Research Group, Institute of Infection, Immunity and Inflammation, Faculty of Medicine, University of Calgary, Calgary, AB, CanadaAllergy and Immunology Section, University of California, San Diego School of Medicine, La Jolla, CA, USAFirestone Institute for Respiratory Health, St. Joseph's Hospital and the Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Leigh
authors.affiliation: Airways Inflammation Research Group, Institute of Infection, Immunity and Inflammation, Faculty of Medicine, University of Calgary, Calgary, AB, CanadaAllergy and Immunology Section, University of California, San Diego School of Medicine, La Jolla, CA, USAFirestone Institute for Respiratory Health, St. Joseph's Hospital and the Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: P M
authors.initials: PM
authors.lastname: O'Byrne
authors.affiliation: Airways Inflammation Research Group, Institute of Infection, Immunity and Inflammation, Faculty of Medicine, University of Calgary, Calgary, AB, CanadaAllergy and Immunology Section, University of California, San Diego School of Medicine, La Jolla, CA, USAFirestone Institute for Respiratory Health, St. Joseph's Hospital and the Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Newton
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000485:Allergens / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy / Q000235:genetics*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D019819:Budesonide / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D018592:Cross-Over Studies; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D022021:Tacrolimus Binding Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000099159:Tacrolimus Binding Protein 5
chemical_list: D000305:Adrenal Cortex Hormones; D000485:Allergens; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D019819:Budesonide; D054638:Dual Specificity Phosphatase 1; D012333:RNA, Messenger; D022021:Tacrolimus Binding Proteins; D014157:Transcription Factors; D000099159:Tacrolimus Binding Protein 5; C404226:TSC22D3 protein, human