Differentiated transplant derived airway epithelial cell cytokine secretion is not regulated by cyclosporine
While lung transplantation is an increasingly utilized therapy for advanced lung diseases, chronic rejection in the form of Bronchiolitis Obliterans Syndrome (BOS) continues to result in significant allograft dysfunction and patient mortality. Despite correlation of clinical events with eventual development of BOS, the causative pathophysiology remains unknown.
Airway epithelial cells within the region of inflammation and fibrosis associated with BOS may have a participatory role.
Methods: Transplant derived airway epithelial cells differentiated in air liquid interface culture were treated with IL-1beta and/or cyclosporine, after which secretion of cytokines and growthfactor and gene expression for markers of epithelial to mesenchymal transition were analyzed.
Results: Secretion of IL-6, IL-8, and TNF-alpha, but not TGF-beta1, was increased by IL-1beta stimulation. In contrast to previous studies using epithelial cells grown in submersion culture, treatment of differentiated cells in ALI culture with cyclosporine did not elicit cytokine or growth factor secretion, and did not alter IL-6, IL-8, or TNF-alpha production in response to IL-1beta treatment.
Neither IL-1beta nor cyclosporine elicited expression of markers of the epithelial to mesenchymal transition E-cadherin, EDN-fibronectin, and alpha-smooth muscle actin.
Conclusion: Transplant derived differentiated airway epithelial cell IL-6, IL-8, and TNF-alpha secretion is not regulated by cyclosporine in vitro; these cells thus may participate in local inflammatory responses in the setting of immunosuppression.
Further, treatment with IL-1beta did not elicit gene expression of markers of epithelial to mesenchymal transition. These data present a model of differentiated airway epithelial cells that may be useful in understanding epithelial participation in airway inflammation and allograft rejection in lung transplantation.
Author: Timothy FlorethEric SternYingli TuRandi SternEdward GarritySangeeta BhoradeSteven White
Credits/Source: Respiratory Research 2011, 12:44
Published on: 2011-04-10
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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