Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.
Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.
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DOI：
10.1371/journal.pone.0064281
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gabazza EC
中科院分区：
文献类型：
--
作者：
Yasukawa A;Hosoki K;Toda M;Miyake Y;Matsushima Y;Matsumoto T;Boveda-Ruiz D;Gil-Bernabe P;Nagao M;Sugimoto M;Hiraguchi Y;Tokuda R;Naito M;Takagi T;D'Alessandro-Gabazza CN;Suga S;Kobayashi T;Fujisawa T;Taguchi O;Gabazza EC
嗜酸性粒细胞炎症和气道重塑，包括上皮下纤维化和肌成纤维细胞增生是支气管哮喘的特征性病理改变。上皮间质转化（EMT）在气道重塑中起着关键作用。在这项研究中，我们假设嗜酸性粒细胞浸润促进支气管哮喘气道重塑。为了证明这一假设，我们评估了EMT的嗜酸性粒细胞在体外和体内研究的影响。在接受气管内滴注小鼠骨髓来源的嗜酸性粒细胞的小鼠中以及与从健康个体新鲜纯化的嗜酸性粒细胞或与嗜酸性粒细胞白血病细胞系共培养的人支气管上皮细胞中评估了EMT。气管内滴注嗜酸性粒细胞与增强的支气管炎症和纤维化以及增加的肺生长因子浓度相关。与对照组相比，用转化生长因子（TGF）-β1 siRNA预处理的嗜酸性粒细胞滴注的小鼠支气管壁纤维化减少。EMT在与人嗜酸性粒细胞共培养的支气管上皮细胞中被诱导，其与支气管上皮细胞中TGF-β1和Smad 3磷酸化的表达增加有关。用抗TGF-β1抗体处理可阻断支气管上皮细胞的EMT。嗜酸性粒细胞在支气管上皮细胞中诱导EMT，表明它们在气道重塑的发病机制中起作用。
Eosinophilic inflammation and remodeling of the airways including subepithelial fibrosis and myofibroblast hyperplasia are characteristic pathological findings of bronchial asthma. Epithelial to mesenchymal transition (EMT) plays a critical role in airway remodelling. In this study, we hypothesized that infiltrating eosinophils promote airway remodelling in bronchial asthma. To demonstrate this hypothesis we evaluated the effect of eosinophils on EMT by in vitro and in vivo studies. EMT was assessed in mice that received intra-tracheal instillation of mouse bone marrow derived eosinophils and in human bronchial epithelial cells co-cultured with eosinophils freshly purified from healthy individuals or with eosinophilic leukemia cell lines. Intra-tracheal instillation of eosinophils was associated with enhanced bronchial inflammation and fibrosis and increased lung concentration of growth factors. Mice instilled with eosinophils pre-treated with transforming growth factor(TGF)-β1 siRNA had decreased bronchial wall fibrosis compared to controls. EMT was induced in bronchial epithelial cells co-cultured with human eosinophils and it was associated with increased expression of TGF-β1 and Smad3 phosphorylation in the bronchial epithelial cells. Treatment with anti-TGF-β1 antibody blocked EMT in bronchial epithelial cells. Eosinophils induced EMT in bronchial epithelial cells, suggesting their contribution to the pathogenesis of airway remodelling.
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影响因子：
15.3
作者：
Jacobsen, Elizabeth A.;Ochkur, Sergei I.;Pero, Ralph S.;Taranova, Anna G.;Protheroe, Cheryl A.;Colbert, Dana C.;Lee, Nancy A.;Lee, James J.
通讯作者：
Lee, James J.
DOI：
10.1165/ajrcmb.17.3.2733
发表时间：
1997-09-01
影响因子：
6.4
作者：
Minshall, EM;Leung, DYM;Hamid, Q
通讯作者：
Hamid, Q
DOI：
10.1164/rccm.200205-414oc
发表时间：
2003-01-01
影响因子：
24.7
作者：
Payne, DNR;Rogers, AV;Jeffery, PK
通讯作者：
Jeffery, PK
影响因子：
3.9
作者：
Gauldie, J.;Bonniaud, P.;Kolb, M.
通讯作者：
Kolb, M.
影响因子：
14.2
作者：
Sagara, H;Okada, T;Nakao, A
通讯作者：
Nakao, A