Epithelial SERPINB10, a novel marker of airway eosinophilia in asthma, contributes to allergic airway inflammation
Epithelial SERPINB10, a novel marker of airway eosinophilia in asthma, contributes to allergic airway inflammation
复制标题
上皮 SERPINB10 是哮喘气道嗜酸性粒细胞增多的新标志物，可导致过敏性气道炎症。
DOI：
10.1152/ajplung.00362.2017
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发表时间：
2019-01-01
影响因子：
4.9
通讯作者：
Zhen, Guohua
中科院分区：
文献类型：
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作者：
Mo, Yuqing;Zhang, Kan;Zhen, Guohua
丝氨酸肽酶抑制剂，进化枝B，成员10（SERPINB 10）表达在IL-13刺激的人支气管上皮细胞和过敏性气道炎症的鼠模型中增加。然而，SERPINB 10在哮喘中的作用仍然未知。我们在动物模型中研究了哮喘患者上皮细胞SERPINB 10表达与气道嗜酸性粒细胞增多之间的关系以及SerpinB 10在过敏性气道炎症中的作用。与健康对照组（n = 25）相比，哮喘受试者（n = 60）的上皮细胞SERPINB 10 mRNA和蛋白表达显著增加。上皮细胞SERPINB 10 mRNA水平与哮喘患者气道高反应性（AHR）和反映气道嗜酸性粒细胞的三个参数（痰液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气一氧化氮分数）显著相关。此外，上皮SERPINB 10表达与2型状态的上皮基因特征（CLCA 1、POR 4和SERPINB 2）密切相关。在空气-液体界面培养的正常人支气管上皮细胞中，SERPINB 10的敲低通过抑制p38 MAPK的活化来抑制IL-13刺激的骨膜蛋白（由POST 3编码）和CCL 26（嗜酸细胞活化趋化因子-3）的表达。在哮喘患者中，上皮细胞CCL 26 mRNA水平与SERPINB 10表达相关。气道敲低Serpinb 10可减轻过敏性气道疾病小鼠模型中的AHR、气道嗜酸性粒细胞增多以及骨膜蛋白和Ccl 26的表达。总之，上皮SERPINB 10是哮喘气道嗜酸性粒细胞增多症的一种新标志物。上皮SERPINB 10至少部分通过调节骨膜蛋白和CCL 26的表达而促成过敏性气道嗜酸性粒细胞炎症。
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 an 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.