title: Expression of IL-4 receptor alpha on smooth muscle cells is not necessary for development of experimental allergic asthma.
abstract: BACKGROUND
  Airflow in the lungs of patients with allergic asthma is impaired by excessive mucus production and airway smooth muscle contractions. Elevated levels of the cytokines IL-4 and IL-13 are associated with this pathology. In vitro studies have suggested that IL-4 receptor alpha (IL-4Ralpha) signaling on smooth muscle cells is critical for airway inflammation and airway hyperresponsiveness.
  
  
  OBJECTIVE
  To define the contribution of IL-4 and IL-13 to the onset of asthmatic pathology, the role of their key receptor IL-4Ralpha in smooth muscle cells was examined in vivo.
  
  
  METHODS
  By using transgenic smooth muscle myosin heavy chain(cre)IL-4Ralpha(-/lox) mice deficient in IL-4Ralpha in smooth muscle cells, in vivo effects of impaired IL-4Ralpha signaling in smooth muscle cells on the outcome of asthmatic disease were investigated for the first time. Allergic asthma was introduced in mice by repeated sensitization with ovalbumin/aluminum hydroxide on days 0, 7, and 14, followed by intranasal allergen challenge on days 21 to 23. Mice were investigated for the presence of airway hyperresponsiveness, airway inflammation, allergen-specific antibody production, T(h)2-type cytokine responses, and lung pathology.
  
  
  RESULTS
  Airway hyperresponsiveness, airway inflammation, mucus production, T(h)2 cytokine production, and specific antibody responses were unaffected in smooth muscle myosin heavy chain(cre)IL-4Ralpha(-/lox) mice compared with control animals.
  
  
  CONCLUSIONS
  The impairment of IL-4Ralpha on smooth muscle cells had no effect on major etiologic markers of allergic asthma. These findings suggest that IL-4Ralpha responsiveness in airway smooth muscle cells during the early phase of allergic asthma is not, as suggested, necessary for the outcome of the disease.
authors.affiliation: Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Health Sciences Faculty, University of Cape Town and International Centre for Genetic Engineering and Biotechnology, Cape Town, South Africa.
authors.forename: Frank
authors.initials: F
authors.lastname: Kirstein
authors.forename: William G C
authors.initials: WG
authors.lastname: Horsnell
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Kuperman
authors.forename: Xiaozhu
authors.initials: X
authors.lastname: Huang
authors.forename: David J
authors.initials: DJ
authors.lastname: Erle
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Lopata
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
mesh_terms: D000485:Allergens / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D000485:Allergens; D015415:Biomarkers; D018793:Interleukin-13; D015847:Interleukin-4; D011956:Receptors, Cell Surface; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit