Expression of IL-4 receptor α on smooth muscle cells is not necessary for development of experimental allergic asthma
Kirstein, Frank, Horsnell, William G.C., Kuperman, Douglas A., Huang, Xiaozhu, Erle, David J., Lopata, Andreas L., and Brombacher, Frank (2010) Expression of IL-4 receptor α on smooth muscle cells is not necessary for development of experimental allergic asthma. The Journal of Allergy and Clinical Immunology, 126 (2). pp. 347-354.
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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 α (IL-4Rα) 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-4Rα in smooth muscle cells was examined in vivo. Methods
By using transgenic smooth muscle myosin heavy chaincreIL-4Rα-/lox mice deficient in IL-4Rα in smooth muscle cells, in vivo effects of impaired IL-4Rα 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, Th2-type cytokine responses, and lung pathology. Results
Airway hyperresponsiveness, airway inflammation, mucus production, Th2 cytokine production, and specific antibody responses were unaffected in smooth muscle myosin heavy chaincreIL-4Rα-/lox mice compared with control animals. Conclusion
The impairment of IL-4Rα on smooth muscle cells had no effect on major etiologic markers of allergic asthma. These findings suggest that IL-4Rα responsiveness in airway smooth muscle cells during the early phase of allergic asthma is not, as suggested, necessary for the outcome of the disease.
|Item Type:||Article (Refereed Research - C1)|
|Keywords:||smooth muscle cell, allergy, asthma, cytokine receptors, IL-4, IL-13, gene-deficient mice|
|Date Deposited:||30 Nov 2010 01:34|
|FoR Codes:||06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060199 Biochemistry and Cell Biology not elsewhere classified @ 100%|
|SEO Codes:||92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%|
|Citation Count from Web of Science||