ePrints

Inflammation and Epithelial to Mesenchymal Transition in Lung Transplant Recipients: Role in Dysregulated Epithelial Wound Repair

Lookup NU author(s): Dr Lee Borthwick, Marta Gorowiec, Dr Malcolm Brodlie, Professor Christopher WardORCiD, Dr James Lordan, Emeritus Professor John Kirby, Professor Andrew FisherORCiD

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

Abstract

Epithelial to mesenchymal transition (EMT) has been implicated in the pathogenesis of obliterative bronchiolitis (OB) after lung transplant. Although TNF-alpha accentuates TGF-beta 1 driven EMT in primary human bronchial epithelial cells (PBECs), we hypothesized that other acute pro-inflammatory cytokines elevated in the airways of patients with OB may also accentuate EMT and contribute to dysregulated epithelial wound repair. PBECs from lung transplant recipients were stimulated with TGF-beta 1 +/- IL-1 beta, IL-8, TNF-alpha or activated macrophages in co-culture and EMT assessed. The quality and rate of wound closure in a standardized model of lung epithelial injury was assessed in response to above stimuli. Co-treatment with TGF-beta 1 + TNF-alpha or IL-1 beta significantly accentuates phenotypic and some functional features of EMT compared to TGF-beta 1 alone. Co-treatment with TGF-beta 1 + TNF-alpha or IL-1 beta accelerates epithelial wound closure however the quality of repair is highly dysregulated. Co-treatment with TGF-beta 1 + IL-8 has no significant effect on EMT or the speed or quality of wound healing. Activated macrophages dramatically accentuate TGF-beta 1-driven EMT and cause dysregulated wound repair. Crosstalk between macrophage-derived acute inflammation in the airway and elevated TGF-beta 1 may favor dysregulated airway epithelial repair and fibrosis in the lung allograft via EMT.

Publication metadata

Author(s): Borthwick LA, McIlroy EI, Gorowiec MR, Brodlie M, Johnson GE, Ward C, Lordan JL, Corris PA, Kirby JA, Fisher AJ

Publication type: Article

Publication status: Published

Journal: American Journal of Transplantation

Year: 2010

Volume: 10

Issue: 3

Pages: 498-509

Print publication date: 05/01/2010

ISSN (print): 1600-6135

ISSN (electronic): 1600-6143

Publisher: Wiley-Blackwell

URL: http://dx.doi.org/10.1111/j.1600-6143.2009.02953.x

DOI: 10.1111/j.1600-6143.2009.02953.x

Altmetrics

Funding

Share