期刊
ALLERGY
卷 75, 期 9, 页码 2267-2278出版社
WILEY
DOI: 10.1111/all.14261
关键词
asthma; hypersensitivity; Protein S; Th1 cells; Th2 cells
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [15K09170]
- Grants-in-Aid for Scientific Research [15K09170] Funding Source: KAKEN
Background Bronchial asthma is a chronic disease characterized by inflammation, obstruction, and hyperresponsiveness of the airways. There is currently no curative therapy for asthma. Type 2 helper T cell response plays a critical role in the pathogenesis of the disease. Protein S is a glycoprotein endowed with anticoagulant, anti-inflammatory, and anti-apoptotic properties. Whether protein S can suppress bronchial asthma and be useful for its therapy is unknown. Methods To address this question here we compared the development of allergen-associated bronchial asthma between wild type and protein S-overexpressing transgenic mice. Mice were sensitized and challenged with ovalbumin. We also evaluated the circulating levels of total and active protein S in patients with bronchial asthma and healthy controls. Results The circulating level of total protein S and of its active form was significantly decreased in patients with bronchial asthma compared to controls. Allergic protein S transgenic mice showed a significant reduction of airway hyperresponsiveness, lung tissue inflammatory cell infiltration, lung levels of Th2 cytokines and IgE compared to their wild-type counterparts. Administration of exogenous human protein S also decreased airway hyperresponsiveness and Th2-mediated lung inflammation in allergic wild-type mice compared with their untreated mouse counterparts. Human protein S significantly shifted the Th1/Th2 balance to Th1 and promoted the secretion of Th1 cytokines (IL-12, tumor necrosis factor-alpha) from dendritic cells. Conclusions These observations suggest the strong protective activity of protein S against the development of allergic bronchial asthma implicating its potential usefulness for the disease treatment.
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