Pseudomonas aeruginosa accentuates epithelial-to-mesenchymal transition in the airway.
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)-β1. P. aeruginosa did not drive or accentuate TGF-β1-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-β1-driven EMT. P. aeruginosa, via the activation of monocytic cells, can accentuate TGF-β1-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.
Borthwick
L A
LA
Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle, UK.
Sunny
S S
SS
Oliphant
V
V
Perry
J
J
Brodlie
M
M
Johnson
G E
GE
Ward
C
C
Gould
K
K
Corris
P A
PA
De Soyza
A
A
Fisher
A J
AJ
D001980:Bronchi / Q000187:drug effects / Q000382:microbiology; D001989:Bronchiolitis Obliterans / Q000382:microbiology; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D016040:Lung Transplantation; D016676:Macrophages, Alveolar / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects; D011552:Pseudomonas Infections / Q000150:complications / Q000378:metabolism; D011550:Pseudomonas aeruginosa; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology
D053773:Transforming Growth Factor beta1