Eosinophil-epithelial cell interactions stimulate the production of MUC5AC mucin and profibrotic cytokines involved in airway tissue remodeling
Eosinophil-epithelial cell interactions stimulate the production of MUC5AC mucin and profibrotic cytokines involved in airway tissue remodeling
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DOI：
10.2500/ajra.2014.28.4018
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发表时间：
2014-03-01
影响因子：
2.6
通讯作者：
Shimizu, Takeshi
中科院分区：
文献类型：
--
作者：
Shimizu, Shino;Kouzaki, Hideaki;Shimizu, Takeshi
背景资料：嗜酸性粒细胞浸润和组织重塑是鼻息肉病和支气管哮喘等慢性气道炎症的共同特征。本研究旨在阐明嗜酸性粒细胞在慢性气道炎症组织重塑中的作用;通过气道上皮细胞系NCI-H292与嗜酸性粒细胞系EoL-1或与人血嗜酸性粒细胞的共培养来检查嗜酸性粒细胞-上皮相互作用。共培养诱导的MUC 5AC粘蛋白、血小板衍生生长因子AB（PDGF-AB）、血管内皮生长因子（VEGF），结果：嗜酸性粒细胞-上皮细胞相互作用显著刺激培养上清液中MUC 5AC、PDGF-AB、VEGF、TGF-β 1和IL-8的分泌。表皮生长因子受体酪氨酸激酶抑制剂AG 1478抑制共培养诱导的MUC 5AC、PDGF-AB、VEGF和IL-8的分泌。针对TGF-α或双调蛋白和泛金属蛋白酶抑制剂GM 6001的中和抗体抑制共培养的NCI-H292细胞的MUC 5AC和双调蛋白的共培养诱导的分泌。NCI-H292细胞与外周血嗜酸性粒细胞的共培养也显着刺激MUC 5AC production.Conclusion：本研究的结果表明，嗜酸性粒细胞上皮细胞的相互作用是重要的嗜酸性粒细胞为主的气道炎症，如发生在鼻息肉病和支气管哮喘的组织重塑的发病机制。
Background: Predominant eosinophil infiltration and tissue remodeling are common characteristics of chronic airway inflammation such as nasal polyposis and bronchial asthma. This study was designed to elucidate the role of eosinophils in tissue remodeling of chronic airway inflammation; eosinophil-epithelial interactions were examined by the coculture of airway epithelial cell line NCI-H292 with the eosinophilic cell line EoL-1 or with human blood eosinophils.Methods: The coculture-induced production of MUC5AC mucin, platelet-derived growth factor AB (PDGF-AB), vascular endothelial growth factor (VEGF), transforming growth factor (TGF) beta1, and interleukin-8 (IL-8) were evaluated by enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction.Results: Eosinophil-epithelial interactions significantly stimulated the secretion of MUC5AC, PDGF-AB, VEGF, TGF-beta1, and IL-8 in culture supernatants. The epidermal growth factor receptor tyrosine kinase inhibitor AG1478 inhibited the coculture-induced secretion of MUC5AC, PDGF-AB, VEGF, and IL-8. Neutralizing antibodies directed against TGF-alpha or amphiregulin and pan-metalloproteinase inhibitor GM6001 inhibited the coculture-induced secretion of MUC5AC and amphiregulin from the cocultured NCI-H292 cells. Coculture of NCI-H292 cells with peripheral blood eosinophils also significantly stimulated MUC5AC production.Conclusion: The results of this study indicate that eosinophil-epithelial cell interactions are important in the pathogenesis of tissue remodeling of eosinophil-predominant airway inflammation such as occurs in nasal polyposis and bronchial asthma.