Suppression of IL-13-Associated Gene Signature in Airway Epithelial Cells By Dexamethasone Is Decreased in Poorly Controlled Asthma
Sunday, March 6, 2016: 4:45 PM
Concourse Foyer (Convention Center)
Karlyn Pollack, BS, Sanford Williams, MS, Kristen Wavell, BS, Debbie-Ann Shirley, MD, John W. Steinke, PhD FAAAAI, Larry Borish, MD FAAAAI, W. Gerald Teague, MD
Rationale: Asthma is associated with the metaplastic transformation of airway epithelial cells (EpC), a process stimulated in part by the cytokine IL-13 that drives mucus hypersecretion and bronchial hyperreactivity.  This IL-13-inducible transformation is associated with the expression of a stereotypic gene signature including SerB2, CLCA1, and periostin and the IL-13-induced expression of these genes is normally suppressed by corticosteroids (CCS).   Poor symptom control in children with asthma may be associated with insensitivity to the anti-inflammatory effects of corticosteroids. We investigated the ability of physiological concentrations of dexamethasone (dex) to inhibition expression of SerB2, CLCA1, and periostin in EpCs obtained from children with controlled (n=3) and poorly-controlled (n=10) asthma.

Methods: Children with asthma underwent bronchoscopy to evaluate refractory wheeze or suspected structural anomalies and grouped according to the level of asthma control by the cACT (childhood asthma control test). Fresh EpC were obtained via endobronchial brushings and cultured in the absence or presence of a physiological concentration of dexamethasone (10-9M) and alterations in gene expression expressed via quantitative PCR. 

Results: Baseline expression of CLCA1 but not periostin or SerB2 was higher (p = 0.04) in children with poorly- versus well controlled asthma. Dexamethasone inhibited the expression of the three IL-13 inducible gene signature products in controlled but not poorly-controlled children with asthma. 

Conclusions: In children with controlled asthma, bronchial EpCs demonstrated CCS-mediated inhibition of the IL-13-inducible gene signature SerB2, CLCA1, and periostin.  In contrast, EpC from poorly-controlled asthmatics failed to show this response.  Severe, poorly-controlled asthma reflects in part corticosteroid non-responsiveness of bronchial epithelial cells.