蛋白S通过调节Th1/Th2平衡来预防过敏性支气管哮喘
2020/03/11
摘要
背景：支气管哮喘是一种以气道炎症、阻塞和高反应性为特征的慢性疾病。目前还没有有效的治疗哮喘的方法。2型辅助T细胞应答在该病的发病机制中起着关键作用。蛋白S是一种具有抗凝、抗炎、抗凋亡等特性的糖蛋白。目前尚不清楚蛋白S是否能抑制支气管哮喘并对其治疗有用。
方法：为了解决这个问题，我们比较了野生型小鼠和过表达蛋白s的转基因小鼠之间过敏原相关支气管哮喘的发展。使用卵清蛋白致敏小鼠。我们还评估了支气管哮喘患者和健康对照组循环中总蛋白S和活性蛋白S的水平。
结果：与对照组相比，支气管哮喘患者的总蛋白S及其活性形式的循环水平明显降低。变应性蛋白S转基因小鼠与野生型小鼠相比，气道高反应性、肺组织炎性细胞浸润、肺组织Th2细胞因子和IgE水平显著降低。与未治疗的小鼠相比，外源性人蛋白S也能降低过敏性野生型小鼠的气道高反应性和th2介导的肺部炎症。人类蛋白S显著Th1/Th2平衡转向Th1和促进了树突状细胞Th1型细胞因子的分泌(白介素12、肿瘤坏死因子-α)。
结论：这些观察结果提示，蛋白S对变应性支气管哮喘的发生具有很强的保护作用，这暗示了其对该病治疗的潜在价值。
Protein S protects against allergic bronchial asthma by modulating Th1/Th2 balance.
Asayama K, Kobayashi T, D’Alessandro Gabazza CN, Toda M, Yasuma T,
Fujimoto H, Okano T, Saiki H, Takeshita A, Fujiwara K, Fridman D'Alessandro V, Nishihama K, Totoki T, Inoue R, Takei Y, Gabazza EC,
Abstract
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 to 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-α) 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.
背景：支气管哮喘是一种以气道炎症、阻塞和高反应性为特征的慢性疾病。目前还没有有效的治疗哮喘的方法。2型辅助T细胞应答在该病的发病机制中起着关键作用。蛋白S是一种具有抗凝、抗炎、抗凋亡等特性的糖蛋白。目前尚不清楚蛋白S是否能抑制支气管哮喘并对其治疗有用。
方法：为了解决这个问题，我们比较了野生型小鼠和过表达蛋白s的转基因小鼠之间过敏原相关支气管哮喘的发展。使用卵清蛋白致敏小鼠。我们还评估了支气管哮喘患者和健康对照组循环中总蛋白S和活性蛋白S的水平。
结果：与对照组相比，支气管哮喘患者的总蛋白S及其活性形式的循环水平明显降低。变应性蛋白S转基因小鼠与野生型小鼠相比，气道高反应性、肺组织炎性细胞浸润、肺组织Th2细胞因子和IgE水平显著降低。与未治疗的小鼠相比，外源性人蛋白S也能降低过敏性野生型小鼠的气道高反应性和th2介导的肺部炎症。人类蛋白S显著Th1/Th2平衡转向Th1和促进了树突状细胞Th1型细胞因子的分泌(白介素12、肿瘤坏死因子-α)。
结论：这些观察结果提示，蛋白S对变应性支气管哮喘的发生具有很强的保护作用，这暗示了其对该病治疗的潜在价值。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(Allergy 2020 Mar 07)
(Allergy 2020 Mar 07)
Protein S protects against allergic bronchial asthma by modulating Th1/Th2 balance.
Asayama K, Kobayashi T, D’Alessandro Gabazza CN, Toda M, Yasuma T,
Fujimoto H, Okano T, Saiki H, Takeshita A, Fujiwara K, Fridman D'Alessandro V, Nishihama K, Totoki T, Inoue R, Takei Y, Gabazza EC,
Abstract
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 to 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-α) 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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多种过敏原特异性IgE抗体之间的连通性及其与重症哮喘的关系
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哮喘患儿鼻病毒A和C刺激淋巴细胞的差异基因表达
