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Inflammation and Epithelial to Mesenchymal Transition in Lung Transplant Recipients: Role in Dysregulated Epithelial Wound Repair
| Content Provider | Scilit |
|---|---|
| Author | Borthwick, L. A. McIlroy, E. I. Gorowiec, M. R. Brodlie, Malcolm Johnson, G. E. Ward, Chris Lordan, J. L. Corris, P. A. Kirby, J. A. Fisher, A. J. |
| Copyright Year | 2010 |
| Description | Journal: American Journal of Transplantation Epithelial to mesenchymal transition (EMT) has been implicated in the pathogenesis of obliterative bronchiolitis (OB) after lung transplant. Although TNF-alpha accentuates TGF-beta1 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-beta1+/-IL-1beta, 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-beta1+TNF-alpha or IL-1beta significantly accentuates phenotypic and some functional features of EMT compared to TGF-beta1 alone. Co-treatment with TGF-beta1+TNF-alpha or IL-1beta accelerates epithelial wound closure however the quality of repair is highly dysregulated. Co-treatment with TGF-beta1+IL-8 has no significant effect on EMT or the speed or quality of wound healing. Activated macrophages dramatically accentuate TGF-beta1-driven EMT and cause dysregulated wound repair. Crosstalk between macrophage-derived acute inflammation in the airway and elevated TGF-beta1 may favor dysregulated airway epithelial repair and fibrosis in the lung allograft via EMT. |
| Related Links | http://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2009.02953.x/pdf |
| Ending Page | 509 |
| Page Count | 12 |
| Starting Page | 498 |
| e-ISSN | 16006143 |
| DOI | 10.1111/j.1600-6143.2009.02953.x |
| Journal | American Journal of Transplantation |
| Issue Number | 3 |
| Volume Number | 10 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2010-03-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: American Journal of Transplantation Cell Tissue Engineering Bronchiolitis Obliterans Syndrome Epithelial Mesenchymal Transition Obilterative Bronchiolitis Transforming Growth Factor‐ß1 Tumor Necrosis Factor Alpha |
| Content Type | Text |
| Resource Type | Article |
