Clarification of the underlying mechanism of allergic diseases targeting the signal pathways of the involved cytokines

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We found in this study that periostin, an extracellular matrix protein, is a component of fibrosis in bronchial asthma and that pendrin, an anion exchanger, is a mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease (COPD). In the former project, we obtained the following results. (1) Upon stimulation of IL-4/IL-13, lung fibroblasts secreted periostin. (2) Periostin was deposited in the fibrotic legions of asthma. (3) Periostin bound to other matrix proteins such as tenascin-C, fibronectin, and collagen V. These results suggest that periostin is secreted from lung fibroblasts stimulated with IL-4/IL-13 in bronchial asthma and is involved in fibrosis of asthma by binding to other matrix proteins. In the latter project, we obtained the following results. (1) Bronchial epithelial cells cultured by the air-interface method in the presence of IL-13 differentiated into mucus-producing cells and these cell expressed pendrin. (2) Expression of pendrin was up-regulated in lung tissues of bronchial asthma and COPD. (3) Enforced expression of pendrin in airway cells caused mucus production. (4) Enforced expression of pendrin into mouse lungs caused mucus production with infiltration of neutrophils. These results suggest that pendrin is induced in the lung tissues of bronchial asthma and COPD and is involved in mucus production in these diseases. Fibrosis and mucus production are deeply correlated with morbidity and mortality of bronchial asthma and COPD. Therefore, the present results are useful to comprehend the whole molecular mechanism of fibrosis and mucus production in bronchial asthma and COPD and to develop therapeutic reagents against these phenotypes.