title: Glucocorticoid-induced changes in gene expression of airway smooth muscle in patients with asthma.
abstract: BACKGROUND
  Glucocorticoids are the mainstay of asthma therapy. However, it is unclear whether the benefits of glucocorticoids in asthma are merely based on antiinflammatory properties. Glucocorticoids may also alter gene expression of airway smooth muscle (ASM). We hypothesized that the gene expression profile of the ASM layer in endobronchial biopsies of patients with asthma is altered by oral glucocorticoid therapy as compared with placebo.
  
  
  OBJECTIVE
  First, we investigated the change in ASM transcriptomic profile in endobronchial biopsies after 14 days of oral glucocorticoid therapy. Second, we investigated the association between changes in ASM transcriptomic profile and lung function.
  
  
  METHODS
  Twelve steroid-free patients with atopic asthma were included in this double-blind intervention study. Endobronchial biopsies were taken before and after 14 days of oral prednisolone (n = 6) or placebo (n = 6). RNA of laser-dissected ASM was sequenced (RNA-Seq) using GS FLX+ (454/Roche). Gene networks were identified by Ingenuity Pathway Analysis. RNA-Seq reads were assumed to follow a negative binomial distribution. At the current sample size the estimated false discovery rate was approximately 3%.
  
  
  RESULTS
  Fifteen genes were significantly changed by 14 days of oral prednisolone. Two of these genes (FAM129A, SYNPO2) were associated with airway hyperresponsiveness (provocative concentration of methacholine causing a 20% drop in FEV1: r = -0.740, P < 0.01; r = -0.746, P < 0.01). Pathway analysis revealed three gene networks that were associated with cellular functions including cellular growth, proliferation, and development.
  
  
  CONCLUSIONS
  Oral prednisolone changes the transcriptomic profile of the ASM layer in asthma. This indicates that in parallel to antiinflammatory properties, glucocorticoids also exert effects on gene expression of ASM, which is correlated with improved airway function.
authors.affiliation: Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. c.y.yick@amc.uva.nl
authors.forename: Ching Yong
authors.initials: CY
authors.lastname: Yick
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Peter W
authors.initials: PW
authors.lastname: Kunst
authors.forename: Katrien
authors.initials: K
authors.lastname: Grünberg
authors.forename: Thais
authors.initials: T
authors.lastname: Mauad
authors.forename: Kees
authors.initials: K
authors.lastname: Fluiter
authors.forename: Elisabeth H
authors.initials: EH
authors.lastname: Bel
authors.forename: René
authors.initials: R
authors.lastname: Lutter
authors.forename: Frank
authors.initials: F
authors.lastname: Baas
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Sterk
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects*; D011239:Prednisolone / Q000494:pharmacology*; D012129:Respiratory Function Tests / Q000379:methods / Q000706:statistics & numerical data; D059467:Transcriptome / Q000187:drug effects; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D011239:Prednisolone