Expression of IL-4 receptor alpha on smooth muscle cells is not necessary for development of experimental allergic asthma.
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.
Kirstein
Frank
F
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.
Horsnell
William G C
WG
Kuperman
Douglas A
DA
Huang
Xiaozhu
X
Erle
David J
DJ
Lopata
Andreas L
AL
Brombacher
Frank
F
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
D000485:Allergens; D015415:Biomarkers; D018793:Interleukin-13; D015847:Interleukin-4; D011956:Receptors, Cell Surface; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit