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Growth factor upregulation during obliterative bronchiolitis in the mouse model
Robert M Aris1, Sean Walsh, Worakij Chalermskulrat
1Division of Pulmonary Medicine, Department of Medicine, 420 Burnett-Womack Building, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7524, USA. aris@med.unc.edu
American Journal of Respiratory and Critical Care Medicine
|August 3, 2002
Summary
Obliterative bronchiolitis (OB) involves increased growth factor expression after lung transplants. Blocking tumor necrosis factor-alpha (TNF-alpha) reduced injury and obstruction in a mouse model, suggesting a potential treatment for chronic allograft rejection.
Area of Science:
- Immunology
- Transplantation Biology
- Molecular Biology
Background:
- Obliterative bronchiolitis (OB) is a primary cause of lung transplant failure.
- Understanding the molecular mechanisms of OB is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the upregulation of specific growth factors during OB in a mouse heterotopic trachea model.
- To evaluate the therapeutic potential of blocking tumor necrosis factor-alpha (TNF-alpha) in ameliorating OB.
Main Methods:
- Comparison of isografts and allografts in cyclosporine-treated mice.
- Gene expression analysis using reverse transcription polymerase chain reaction (RT-PCR) for various growth factors (PDGF, FGF, TGF-beta, TNF-alpha, etc.).
- Assessment of OB severity and the effect of TNF-alpha blockade using a soluble receptor (human TNFR:Fc).
Main Results:
- Significant upregulation of transforming growth factor-beta, TNF-alpha, endothelin-1, and insulin-like growth factor-1 in allografts compared to isografts.
- Transient increase in FGF-1, FGF-2, and PDGF-B expression in allografts.
- TNF-alpha blockade significantly reduced epithelial injury and lumenal obstruction in the OB model.
Conclusions:
- OB is associated with the increased expression of multiple growth factors.
- Targeting TNF-alpha may be a promising strategy for managing OB and improving lung transplant outcomes.