title: Increased expression of interleukin-9, interleukin-9 receptor, and the calcium-activated chloride channel hCLCA1 in the upper airways of patients with cystic fibrosis.
abstract: OBJECTIVE
  Mucus overproduction is commonly found in airway disease in patients with cystic fibrosis. Interleukin-9 (IL-9) has been shown to mediate airway hyper-responsiveness and mucus overproduction. Recently, the calcium-activated chloride channel hCLCA1 has been described to be upregulated by IL-9 and has been thought to regulate the expression of soluble gel-forming mucins. We sought to examine the expression of IL-9, interleukin-9 receptor (IL-9R), and hCLCA1 in the upper airway of patients with cystic fibrosis in comparison to healthy control subjects and to demonstrate the relationship of IL-9, IL-9R, and hCLCA1 expression with mucus production.
  
  
  METHODS
  Prospective design.
  
  
  METHODS
  Biopsy samples from nasal polyps of four patients with cystic fibrosis, nasal mucosa of six patients with cystic fibrosis, sinus mucosa of eight patients with cystic fibrosis, and nasal mucosa of six healthy control subjects were stained with periodic acid-Schiff (PAS) to identify mucus glycoconjugates. IL-9, IL-9R, and hCLCA1 expression was determined by immunocytochemical study.
  
  
  RESULTS
  We demonstrated significant increases in IL-9, IL-9R, and hCLCA1 immunoreactivity in the mucosa of patients with cystic fibrosis compared with that found in control subjects (P <.05). There were no significant differences between the different locations (nasal polyps, nasal mucosa, and sinus mucosa) in the patient group (P >.05). We also observed a significant increase in the number of mucus-producing cells in biopsy specimens from patients with cystic fibrosis in comparison to control subjects. A positive correlation was found between hCLCA1-positive cells and IL-9-positive cells (correlation coefficient [r] = 0.79, P <.05) or IL-9R-positive cells (r = 0.92, P <.05). Moreover, a positive correlation was also present between PAS-positive (mucus-producing) cells and hCLCA1-positive cells (r = 0.64, P <.05) or IL-9R-positive cells (r = 0.64, P <.05).
  
  
  CONCLUSIONS
  Increased expression of IL-9 and IL-9R, as well as upregulation of hCLCA1, in mucus-overproducing epithelium of patients with cystic fibrosis supports the hypothesis that IL-9 contributes to mucus overproduction in cystic fibrosis. Expression of hCLCA1 may also be responsible, in part, for the overproduction of mucus. These preliminary findings suggest that hCLCA1 might be an interesting new therapeutic target to control mucus overproduction in airway disease in patients with cystic fibrosis.
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hauber
authors.forename: John J
authors.initials: JJ
authors.lastname: Manoukian
authors.forename: Lily H P
authors.initials: LH
authors.lastname: Nguyen
authors.forename: Steven E
authors.initials: SE
authors.lastname: Sobol
authors.forename: Roy C
authors.initials: RC
authors.lastname: Levitt
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Holroyd
authors.forename: Noel G
authors.initials: NG
authors.lastname: McElvaney
authors.forename: Siobhan
authors.initials: S
authors.lastname: Griffin
authors.forename: Qutayba
authors.initials: Q
authors.lastname: Hamid
mesh_terms: D001706:Biopsy; D018118:Chloride Channels / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000276:immunology* / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D016906:Interleukin-9 / Q000378:metabolism*; D009077:Mucins / Q000378:metabolism; D009093:Mucus / Q000276:immunology; D009297:Nasal Mucosa / Q000276:immunology / Q000473:pathology; D009298:Nasal Polyps / Q000276:immunology / Q000473:pathology; D018123:Receptors, Interleukin / Q000378:metabolism*; D053651:Receptors, Interleukin-9; D012016:Reference Values; D020545:Respiratory Mucosa / Q000276:immunology* / Q000473:pathology; D012852:Sinusitis / Q000276:immunology / Q000473:pathology
chemical_list: C492109:CLCA1 protein, human; D018118:Chloride Channels; C508045:IL9R protein, human; D016906:Interleukin-9; D009077:Mucins; D018123:Receptors, Interleukin; D053651:Receptors, Interleukin-9