上皮SERPINB10是哮喘气道嗜酸性粒细胞增多的新标志物，增加气道过敏性炎症
2018/11/14
摘要
丝氨酸肽酶抑制剂B支链成员10(SERPINB10)在由IL-13刺激的人支气管上皮细胞和小鼠过敏性气道炎症模型中的表达增加。然而，SERPINB10在哮喘中的作用尚不清楚。我们检测了哮喘患者中上皮SERPINB10表达与气道嗜酸性粒细胞的关系，以及Serpinb10在变应性气道炎症动物模型中的作用。哮喘患者（n=60）SERPINB10 mRNA和蛋白表达显著高于健康对照组（n=25）。上皮型SERPINB10 mRNA水平与气道高反应性(AHR)显著相关，反映气道嗜酸性粒细胞病的三个参数包括哮喘患者痰嗜酸性粒细胞百分比、支气管粘膜下层嗜酸性粒细胞数量和呼出NO含量。此外，上皮SERPINB10的表达与T2型哮喘的上皮基因特征（CLCA1、POSTN和SERPINB2）密切相关。在气液界面培养的正常人支气管上皮细胞中，SERPINB10的基因敲除通过抑制p38 MAPK的激活抑制IL-13刺激的骨膜蛋白(POSTN编码)和CCL26(eotaxin-3)的表达。哮喘患者的上皮细胞CL26 mRNA水平与SurPnB10表达相关。Serpinb10的气道基因敲除减轻了过敏性气道疾病小鼠模型的AHR、气道嗜酸性粒细胞增多以及骨膜蛋白和Ccl26的表达。总之，上皮SurPnB10是哮喘气道嗜酸性粒细胞增多症的新标志物。上皮SERPINB10通过调节骨膜蛋白和CCL26的表达，至少部分参与了过敏性气道嗜酸性炎症。
Epithelial SERPINB10, a novel marker of airway eosinophilia in asthma, contributes to allergic airway inflammation.
Mo Y, Zhang K, Feng Y, Yi L, Liang Y, Wu W, Zhao JP, Zhang Z, Xu Y, Hu Q, He J, Zhen G.
Abstract
Serine peptidase inhibitor, clade B, member 10 (SERPINB10) expression is increased in IL-13-stimulated human bronchial epithelial cells and in a murine model of allergic airway inflammation. However, the role of SERPINB10 in asthma remains unknown. We examined the association between epithelial SERPINB10 expression and airway eosinophilia in subjects with asthma and the role of Serpinb10 in allergic airway inflammation in animal model. Epithelial SERPINB10 mRNA and protein expression were markedly increased in subjects with asthma ( n = 60) compared with healthy controls ( n = 25). Epithelial SERPINB10 mRNA levels were significantly correlated with airway hyperresponsiveness (AHR), and three parameters reflecting airway eosinophilia including the percentage of sputum eosinophils, the number of eosinophils in bronchial submucosa, and fraction of exhaled nitric oxide in subjects with asthma. Moreover, epithelial SERPINB10 expression was strongly correlated with the epithelial gene signature ( CLCA1, POSTN and SERPINB2) for type 2 status. In normal human bronchial epithelial cells cultured at air-liquid interface, knockdown of SERPINB10 suppressed IL-13-stimulated periostin (encoded by POSTN) and CCL26 (eotaxin-3) expression by inhibiting the activation of p38 MAPK. Epithelial CCL26 mRNA levels were correlated with SERPINB10 expression in subjects with asthma. Airway knockdown of Serpinb10 alleviated AHR, airway eosinophilia and the expression of periostin and Ccl26 in a murine model of allergic airway disease. Taken together, epithelial SERPINB10 is a novel marker for airway eosinophilia in asthma. Epithelial SERPINB10 contributes to allergic airway eosinophilic inflammation, at least in part, by regulating the expression of periostin and CCL26.
丝氨酸肽酶抑制剂B支链成员10(SERPINB10)在由IL-13刺激的人支气管上皮细胞和小鼠过敏性气道炎症模型中的表达增加。然而，SERPINB10在哮喘中的作用尚不清楚。我们检测了哮喘患者中上皮SERPINB10表达与气道嗜酸性粒细胞的关系，以及Serpinb10在变应性气道炎症动物模型中的作用。哮喘患者（n=60）SERPINB10 mRNA和蛋白表达显著高于健康对照组（n=25）。上皮型SERPINB10 mRNA水平与气道高反应性(AHR)显著相关，反映气道嗜酸性粒细胞病的三个参数包括哮喘患者痰嗜酸性粒细胞百分比、支气管粘膜下层嗜酸性粒细胞数量和呼出NO含量。此外，上皮SERPINB10的表达与T2型哮喘的上皮基因特征（CLCA1、POSTN和SERPINB2）密切相关。在气液界面培养的正常人支气管上皮细胞中，SERPINB10的基因敲除通过抑制p38 MAPK的激活抑制IL-13刺激的骨膜蛋白(POSTN编码)和CCL26(eotaxin-3)的表达。哮喘患者的上皮细胞CL26 mRNA水平与SurPnB10表达相关。Serpinb10的气道基因敲除减轻了过敏性气道疾病小鼠模型的AHR、气道嗜酸性粒细胞增多以及骨膜蛋白和Ccl26的表达。总之，上皮SurPnB10是哮喘气道嗜酸性粒细胞增多症的新标志物。上皮SERPINB10通过调节骨膜蛋白和CCL26的表达，至少部分参与了过敏性气道嗜酸性炎症。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Am J Physiol Lung Cell Mol Physiol. 2018 Nov 1. doi: 10.1152/ajplung.00362.2017.)
(Am J Physiol Lung Cell Mol Physiol. 2018 Nov 1. doi: 10.1152/ajplung.00362.2017.)
Epithelial SERPINB10, a novel marker of airway eosinophilia in asthma, contributes to allergic airway inflammation.
Mo Y, Zhang K, Feng Y, Yi L, Liang Y, Wu W, Zhao JP, Zhang Z, Xu Y, Hu Q, He J, Zhen G.
Abstract
Serine peptidase inhibitor, clade B, member 10 (SERPINB10) expression is increased in IL-13-stimulated human bronchial epithelial cells and in a murine model of allergic airway inflammation. However, the role of SERPINB10 in asthma remains unknown. We examined the association between epithelial SERPINB10 expression and airway eosinophilia in subjects with asthma and the role of Serpinb10 in allergic airway inflammation in animal model. Epithelial SERPINB10 mRNA and protein expression were markedly increased in subjects with asthma ( n = 60) compared with healthy controls ( n = 25). Epithelial SERPINB10 mRNA levels were significantly correlated with airway hyperresponsiveness (AHR), and three parameters reflecting airway eosinophilia including the percentage of sputum eosinophils, the number of eosinophils in bronchial submucosa, and fraction of exhaled nitric oxide in subjects with asthma. Moreover, epithelial SERPINB10 expression was strongly correlated with the epithelial gene signature ( CLCA1, POSTN and SERPINB2) for type 2 status. In normal human bronchial epithelial cells cultured at air-liquid interface, knockdown of SERPINB10 suppressed IL-13-stimulated periostin (encoded by POSTN) and CCL26 (eotaxin-3) expression by inhibiting the activation of p38 MAPK. Epithelial CCL26 mRNA levels were correlated with SERPINB10 expression in subjects with asthma. Airway knockdown of Serpinb10 alleviated AHR, airway eosinophilia and the expression of periostin and Ccl26 in a murine model of allergic airway disease. Taken together, epithelial SERPINB10 is a novel marker for airway eosinophilia in asthma. Epithelial SERPINB10 contributes to allergic airway eosinophilic inflammation, at least in part, by regulating the expression of periostin and CCL26.
上一篇：
氧化应激和巨噬细胞：哮喘和COPD急性加重的驱动力？
下一篇：
高T2型及低T2型哮喘气道免疫功能紊乱的转录组测定
