title: Expression of the IL-4 receptor alpha-subunit is increased in bronchial biopsy specimens from atopic and nonatopic asthmatic subjects.
abstract: BACKGROUND
  Recent studies have provided evidence for increased IL-4 expression in the airways of atopic and nonatopic asthmatic subjects. IL-4 is believed to perform important regulatory roles in asthma; however, the expression of the IL-4 receptor has not been investigated. In this study we examined the mRNA and protein expression of the specific alpha-subunit of the IL-4 receptor (alphaIL-4R) in bronchial biopsy specimens obtained from atopic and nonatopic asthmatic subjects.
  
  
  METHODS
  Asthmatic subjects and nonasthmatic control subjects were recruited, and lung function measurements were performed before bronchoscopy. Endobronchial biopsy specimens were examined for the presence of alphaIL-4R mRNA and immunoreactivity by using in situ hybridization and immunocytochemistry, respectively.
  
  
  RESULTS
  alphaIL-4R mRNA-positive and immunoreactive cells were detected in the epithelium and subepithelium in biopsy specimens from all subjects. Expression of alphaIL-4R mRNA and protein was significantly increased in the epithelium and subepithelium of biopsy specimens from atopic asthmatic subjects compared with atopic control subjects (P <.05 and P <.001, respectively). Epithelial alphaIL-4R mRNA expression and immunoreactivity did not differ significantly between nonatopic asthmatic subjects and nonatopic control subjects. Although the numbers of alphaIL-4R mRNA-positive cells were augmented in the submucosa of intrinsic asthmatic subjects compared with nonatopic control subjects (P <.05), alphaIL-4R immunoreactivity did not differ significantly between these groups. Increased alphaIL-4R immunoreactive signals were also detected in the endothelial cell layer in both atopic and intrinsic asthmatic subjects compared with atopic and nonatopic control subjects, respectively (P <.05). Combined in situ hybridization immunocytochemistry performed on biopsy sections from asthmatic and control subjects demonstrated alphaIL-4R mRNA expression in CD3-positive T cells and tryptasepositive mast cells, with T cells comprising the larger proportion of alphaIL-4R mRNA-positive cells. Numbers of alphaIL-4R mRNA-positive or immunoreactive cells did not correlate with CD3-positive cell numbers, numbers of IL-4 mRNA-positive cells, or indices of pulmonary function.
  
  
  CONCLUSIONS
  These results demonstrate constitutive alphaIL-4R expression in normal airways and enhanced expression in airway tissue from asthmatic individuals.
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
authors.forename: T C
authors.initials: TC
authors.lastname: Kotsimbos
authors.forename: O
authors.initials: O
authors.lastname: Ghaffar
authors.forename: E M
authors.initials: EM
authors.lastname: Minshall
authors.forename: M
authors.initials: M
authors.lastname: Humbert
authors.forename: S R
authors.initials: SR
authors.lastname: Durham
authors.forename: R
authors.initials: R
authors.lastname: Pfister
authors.forename: G
authors.initials: G
authors.lastname: Menz
authors.forename: A B
authors.initials: AB
authors.lastname: Kay
authors.forename: Q A
authors.initials: QA
authors.lastname: Hamid
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology* / Q000378:metabolism*; D001706:Biopsy; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology*; D005541:Forced Expiratory Volume; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000378:metabolism*; D008407:Mast Cells / Q000737:chemistry; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D019948:Receptors, Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D012129:Respiratory Function Tests; D013601:T-Lymphocytes / Q000737:chemistry
chemical_list: D012333:RNA, Messenger; D019948:Receptors, Interleukin-4