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

被引：87

作者：

Borthwick, L. A. ^{[1
]}

McIlroy, E. I. ^{[1
]}

Gorowiec, M. R. ^{[1
]}

Brodlie, M. ^{[1
]}

Johnson, G. E. ^{[1
]}

Ward, C. ^{[1
]}

Lordan, J. L. ^{[1
]}

Corris, P. A. ^{[1
]}

Kirby, J. A. ^{[1
]}

Fisher, A. J. ^{[1
]}

机构：

[1] Newcastle Univ, Inst Cellular Med, Appl Immunobiol & Transplantat Res Grp, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

来源：

AMERICAN JOURNAL OF TRANSPLANTATION | 2010年 / 10卷 / 03期

基金：

英国医学研究理事会;

关键词：

Bronchiolitis obliterans syndrome; epithelial mesenchymal transition; interleukin-1; macrophage; obilterative bronchiolitis; transforming growth factor-ss 1; tumor necrosis factor alpha; BRONCHIOLITIS-OBLITERANS-SYNDROME; GROWTH-FACTOR-BETA; TGF-BETA; PULMONARY-FIBROSIS; SIGNAL-TRANSDUCTION; CELL TRANSITION; KAPPA-B; EXPRESSION; AZITHROMYCIN; DISEASE;

D O I：

10.1111/j.1600-6143.2009.02953.x

中图分类号：

R61 [外科手术学];

学科分类号：

100210 [外科学];

摘要：

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.

引用

页码：498 / 509

页数：12

共 49 条

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