Molecular biologic approach for clarification of the role of bronchial epithelial cells for development of asthma

点击翻译按钮获取中文摘要

It has been known that allergic inflammation at the airway and associated disorder of airway epithelial cells play important roles as causative factors for the airway hyperresponsiveness. In the study, we have studied cytokine production of bronchial epithelial cells in vitro and the effects of these cytokine in vivo to analyze mechanism of relationship between allergic inflammation and airway hyperresponsiveness. We used BEAS-2B cells, a cell line of bronchial epithelial cells transformed by adenovirus-12/SV-40 hybrid and cultured in F-12 medium. SIgA and anti IgA complex induced the release of GM-CSF and IL-8 in a dose-dependent manner. The existence of IgA receptor was demonstrated by flow cytometry analysis using anti-IgA receptor specific monoclonal antibodies. Next, we have established mice asthmatic model sensitized in ovalbumin specific manner and tried to clarify the effects of GM-CSF in vivo. A/J mice were first immunized with OA+Alum, following intranasal sensitization with QA.Intranasal sensitization with OA increased the airway responsiveness to acetylcholine. A pathological study revealed that the treatment with OA replaced the ciliated epithelial cells of the airways with Clara cells. The transnasal administration of GM-CSF neutralizing antibody completely inhibited the increase of airway hyperresponsiveness caused by OA.In conclusion, GM-CSF, which can be produced by bronchial epithelial cells, plays an important role in enhancing airway responsiveness at the site of the airway.