Expression of IL-4 receptor alpha on smooth muscle cells is not necessary for development of experimental allergic asthma.
J Allergy Clin Immunol
; 126(2): 347-54, 2010 Aug.
Article
em En
| MEDLINE
| ID: mdl-20579713
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.CONCLUSION:
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Asma
/
Transdução de Sinais
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Regulação da Expressão Gênica
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Receptores de Superfície Celular
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Miócitos de Músculo Liso
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article