Pseudomonas aeruginosa accentuates epithelial-to-mesenchymal transition in the airway

被引:38
作者
Borthwick, L. A. [1 ]
Sunny, S. S. [1 ]
Oliphant, V. [1 ]
Perry, J. [2 ]
Brodlie, M. [1 ]
Johnson, G. E. [2 ]
Ward, C. [1 ]
Gould, K. [2 ]
Corris, P. A. [1 ,2 ]
De Soyza, A. [1 ,2 ]
Fisher, A. J. [1 ,2 ]
机构
[1] Newcastle Univ, Inst Cellular Med, Appl Immunobiol & Transplantat Res Grp, Newcastle Upon Tyne, Tyne & Wear, England
[2] Freeman Rd Hosp, Dept Cardiopulm Transplantat, Newcastle Upon Tyne, Tyne & Wear, England
基金
英国医学研究理事会;
关键词
Bronchiolitis obliterans syndrome; lung transplantation; macrophages; obliterative bronchiolitis; transforming growth factor-beta 1; BRONCHIOLITIS OBLITERANS SYNDROME; LUNG-TRANSPLANT RECIPIENTS; GROWTH-FACTOR-BETA; AZITHROMYCIN THERAPY; BIOFILM FORMATION; CELL TRANSITION; TGF-BETA; COLONIZATION; EMT; INFLAMMATION;
D O I
10.1183/09031936.00088410
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Epithelial-to-mesenchymal transition (EMT) has been implicated in the dysregulated epithelial wound repair that contributes to obliterative bronchiolitis (OB) after lung transplantation. Acquisition of Pseudomonas aeruginosa in the transplanted airway has been shown to be a risk factor for the development of OB. We investigated the potential of P. aeruginosa to drive EMT in primary bronchial epithelial cells (PBECs) isolated from lung transplant recipients. Changes in the expression of epithelial and mesenchymal markers was assessed in cells challenged with clinical isolates of P. aeruginosa or co-cultured with P. aeruginosa-activated monocytic cells (THP-1) in the presence or absence of transforming growth factor (TGF)-beta 1. P. aeruginosa did not drive or accentuate TGF-beta 1-driven EMT directly. Co-culturing P. aeruginosa-activated THP-1 cells with PBECs did not drive EMT. However, co-culturing P. aeruginosa-activated THP-1 cells with PBECs significantly accentuated TGF-beta 1-driven EMT. P. aeruginosa, via the activation of monocytic cells, can accentuate TGF-beta 1-driven EMT. These in vitro observations may help explain the in vivo clinical observation of a link between acquisition of P. aeruginosa and an increased risk of developing OB.
引用
收藏
页码:1237 / 1247
页数:11
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