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Inflammation and Epithelial to Mesenchymal Transition in Lung Transplant Recipients: Role in Dysregulated Epithelial Wound Repair
Author(s) -
Borthwick L. A.,
McIlroy E. I.,
Gorowiec M. R.,
Brodlie M.,
Johnson G. E.,
Ward C.,
Lordan J. L.,
Corris P. A.,
Kirby J. A.,
Fisher A. J.
Publication year - 2010
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2009.02953.x
Subject(s) - epithelial–mesenchymal transition , medicine , wound healing , lung , inflammation , immunology , tumor necrosis factor alpha , cancer research , pathology , cancer , metastasis
Epithelial to mesenchymal transition (EMT) has been implicated in the pathogenesis of obliterative bronchiolitis (OB) after lung transplant. Although TNF‐α accentuates TGF‐β1 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‐β1 ± IL‐1β, IL‐8, TNF‐α 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‐β1 + TNF‐α or IL‐1β significantly accentuates phenotypic and some functional features of EMT compared to TGF‐β1 alone. Co‐treatment with TGF‐β1 + TNF‐α or IL‐1β accelerates epithelial wound closure however the quality of repair is highly dysregulated. Co‐treatment with TGF‐β1 + IL‐8 has no significant effect on EMT or the speed or quality of wound healing. Activated macrophages dramatically accentuate TGF‐β1‐driven EMT and cause dysregulated wound repair. Crosstalk between macrophage‐derived acute inflammation in the airway and elevated TGF‐β1 may favor dysregulated airway epithelial repair and fibrosis in the lung allograft via EMT.