title: Airway remodeling-associated mediators in moderate to severe asthma: effect of steroids on TGF-beta, IL-11, IL-17, and type I and type III collagen expression.
abstract: BACKGROUND
  Important features of airway remodeling in asthma include the formation of subepithelial fibrosis and increased deposition of types I and III collagen. TGF-beta, IL-11, and IL-17 are profibrotic cytokines involved in the formation of subepithelial fibrosis and are increased in patients with asthma, particularly in those with severe disease.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the effect of corticosteroids on the expression of these profibrotic cytokines and on extracellular matrix deposition.
  
  
  METHODS
  We used immunocytochemistry to measure the expression of TGF-beta, IL-11, IL-17, and collagen types I and III in the airways of patients with mild asthma (n = 9), patients with moderate-to-severe asthma (n = 10), and control subjects without asthma (n = 6). Baseline bronchial biopsy specimens were obtained in all groups. In addition, repeat biopsies were obtained in the patients with moderate-to-severe asthma after a 2-week course of oral corticosteroids.
  
  
  RESULTS
  TGF-beta expression was significantly higher in all groups with asthma, and it did not decrease after treatment with oral corticosteroids. Levels of IL-11 and IL-17 were increased in patients with moderate-to-severe asthma compared with patients with mild asthma and normal controls (P <.05). The expression of these cytokines decreased with oral corticosteroids in the moderate-to-severe group to levels that were comparable to those seen in the patients with mild asthma and in the normal controls (P <.005). Expression of types I and III collagens was higher in the patients with moderate-to-severe asthma than in the patients with mild asthma and the controls (P <.05; P <.001). Treatment with corticosteroids did not decrease the expression of types I and III collagens.
  
  
  CONCLUSIONS
  These results confirm the association of increased levels of TGF-beta, IL-11, IL-17, and types I and III collagens with severe disease and suggest that the failure of cortico-steroids to decrease collagen deposition might be due to persistently elevated TGF-beta expression.
authors.affiliation: Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie, Laval, Quebec, Canada.
authors.forename: Jamila
authors.initials: J
authors.lastname: Chakir
authors.forename: Joanne
authors.initials: J
authors.lastname: Shannon
authors.forename: Sophie
authors.initials: S
authors.lastname: Molet
authors.forename: Motonori
authors.initials: M
authors.lastname: Fukakusa
authors.forename: Jack
authors.initials: J
authors.lastname: Elias
authors.forename: Michel
authors.initials: M
authors.lastname: Laviolette
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Boulet
authors.forename: Qutayba
authors.initials: Q
authors.lastname: Hamid
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D001980:Bronchi / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D024042:Collagen Type I / Q000276:immunology / Q000378:metabolism; D024061:Collagen Type III / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D024022:Fibrillar Collagens / Q000378:metabolism*; D005355:Fibrosis; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D017370:Interleukin-11 / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D016207:Cytokines; D024022:Fibrillar Collagens; D005938:Glucocorticoids; D017370:Interleukin-11; D020381:Interleukin-17; D016212:Transforming Growth Factor beta; D008775:Methylprednisolone