title: IL-9 and its receptor in allergic and nonallergic lung disease: increased expression in asthma.
abstract: BACKGROUND
  Bronchial asthma is a chronic inflammatory disease associated with genetic components. Recently IL-9 has been reported as a candidate gene for asthma and to be associated with bronchial hyperresponsiveness and elevated levels of total serum IgE.
  
  
  OBJECTIVE
  To investigate the contribution of IL-9 to the pathogenesis of asthma, we examined the expression of IL-9 and its receptor (IL-9R) in bronchial tissue from subjects with atopic asthma (n = 10), chronic bronchitis (n = 11), and sarcoidosis (n = 9) and from atopic (n = 7) and nonatopic (n = 10) healthy control subjects.
  
  
  METHODS
  Bronchial biopsy specimens were examined for the presence of IL-9 and IL-9R protein and messenger RNA (mRNA) by immunocytochemistry and in situ hybridization, respectively. To phenotype the cells expressing IL-9 in asthmatic tissue, combined in situ hybridization and immunocytochemistry was also performed.
  
  
  RESULTS
  There was a highly significant difference (P <.001) in the expression of IL-9 mRNA in asthmatic airways (20.6 +/- 4.0 cells/mm of basement membrane) compared with chronic bronchitis (5.6 +/- 4.4), sarcoidosis (2.5 +/- 1.8), atopic control subjects (7.7 +/- 2.2), and healthy control subjects (2.7 +/- 2.3). The number of IL-9 immunoreactive cells was also greater in asthmatic patients compared with the other groups (P <.05). Although the level of IL-9R mRNA expression did not differ in any of the groups (P >.05), IL-9R immunoreactivity was significantly higher in asthmatic compared with control subjects. Furthermore, IL-9 mRNA expression levels were also significantly correlated with FEV(1) (P <.05) and the airway responsiveness to methacholine producing a 20% fall in FEV(1) (P <. 01). The cells expressing IL-9 mRNA in asthmatic tissue were CD3(+) lymphocytes (68%), major basic protein(+) eosinophils (16%), and elastase(+) neutrophils (8%).
  
  
  CONCLUSIONS
  The results of this study demonstrate the potential of IL-9 to be a marker for atopic asthma and furthermore suggest an important role for this cytokine in the pathophysiologic mechanisms of this disease.
authors.affiliation: Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Shimbara
authors.forename: P
authors.initials: P
authors.lastname: Christodoulopoulos
authors.forename: A
authors.initials: A
authors.lastname: Soussi-Gounni
authors.forename: R
authors.initials: R
authors.lastname: Olivenstein
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: R C
authors.initials: RC
authors.lastname: Levitt
authors.forename: N C
authors.initials: NC
authors.lastname: Nicolaides
authors.forename: K J
authors.initials: KJ
authors.lastname: Holroyd
authors.forename: A
authors.initials: A
authors.lastname: Tsicopoulos
authors.forename: J J
authors.initials: JJ
authors.lastname: Lafitte
authors.forename: B
authors.initials: B
authors.lastname: Wallaert
authors.forename: Q A
authors.initials: QA
authors.lastname: Hamid
mesh_terms: D000328:Adult; D001249:Asthma / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism; D001982:Bronchial Diseases / Q000378:metabolism*; D001991:Bronchitis / Q000378:metabolism; D002908:Chronic Disease; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism*; D016906:Interleukin-9 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D053651:Receptors, Interleukin-9; D012016:Reference Values; D012507:Sarcoidosis / Q000378:metabolism
chemical_list: C508045:IL9R protein, human; D016906:Interleukin-9; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053651:Receptors, Interleukin-9