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1 The Applied Immunobiology and Transplantation Research group, The University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, United Kingdom; The Irish Lung Transplant Programme, The Mater Misericordiae Hospital, Dublin, Ireland
2 The Applied Immunobiology and Transplantation Research group, The University of Newcastle-upon-Tyne, United Kingdom
3 The Musculoskeletal Research Group, The University of Newcastle-upon-Tyne, United Kingdom
4 The Irish Lung Transplant Programme, The Mater Misericordiae Hospital, Dublin, Ireland
* To whom correspondence should be addressed. E-mail: chris.ward{at}newcastle.ac.uk.
Rationale:
Obliterative Bronchiolitis (OB), the major cause of chronic lung allograft dysfunction, is characterised by airway neutrophilia, inflammation and remodelling, with progressive fibroproliferation and obliteration of small airways that ultimately leads to patient death. Statins have potential anti-inflammatory effects and have been demonstrated to confer a survival advantage in lung transplant patients. We postulated that the beneficial effects of simvastatin in lung transplantation are in part due to inhibition of the epithelial production of key mediators of neutrophil chemotaxis, inflammation and airway remodelling.
Objective:
To assess the effect of simvastatin on a unique population of primary bronchial epithelial cells (PBECs) derived from stable lung allografts, with specific reference to airway neutrophilia and remodelling.
Methods:
Primary bronchial epithelial cell cultures were stimulated with IL-17 or TGF-
, with and without simvastatin. Supernatant levels of factors critical to driving airway neutrophilia and remodelling were measured.
Results:
IL-17 upregulated IL-8, IL-6, GCSF, GMCSF and VEGF, while TGF- increased IL-6, GM-CSF, MMP-2 and MMP-9. Simvastatin attenuated effects of both IL-17 and TGF-.
Conclusion:
We have demonstrated the ability of simvastatin to attenuate release of airway neutrophilic and remodelling mediators and to inhibit their upregulation by TGF- and IL-17. These data illustrate the potential of simvastatin to alleviate neutrophilic airway inflammation and remodelling in the transplanted lung and may have additional relevance to other neutrophilic airway conditions, such as COPD.
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  P. J. Barnes and B. R. Celli Systemic manifestations and comorbidities of COPD Eur. Respir. J., May 1, 2009; 33(5): 1165 - 1185. [Abstract] [Full Text] [PDF]
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 C Ward, K Eger, J Diboll, D Jones, M A Haniffa, M Brodlie, A Fisher, J L Lordan, P A Corris, and C M U Hilkens Bronchial epithelial cells cultured from clinically stable lung allograft patients promote the development of macrophages from monocytes rather than dendritic cells Thorax, May 1, 2009; 64(5): 430 - 435. [Abstract] [Full Text] [PDF]
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 P. J. Barnes Future Treatments for Chronic Obstructive Pulmonary Disease and Its Comorbidities Proceedings of the ATS, December 1, 2008; 5(8): 857 - 864. [Abstract] [Full Text] [PDF]
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