title: Differentiated transplant derived airway epithelial cell cytokine secretion is not regulated by cyclosporine.
abstract: BACKGROUND
  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-1β and/or cyclosporine, after which secretion of cytokines and growth factor and gene expression for markers of epithelial to mesenchymal transition were analyzed.
  
  
  RESULTS
  Secretion of IL-6, IL-8, and TNF-α, but not TGF-β1, was increased by IL-1β 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-α production in response to IL-1β treatment. Neither IL-1β nor cyclosporine elicited expression of markers of the epithelial to mesenchymal transition E-cadherin, EDN-fibronectin, and α-smooth muscle actin.
  
  
  CONCLUSIONS
  Transplant derived differentiated airway epithelial cell IL-6, IL-8, and TNF-α 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-1β 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.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Floreth
authors.forename: Eric
authors.initials: E
authors.lastname: Stern
authors.forename: Yingli
authors.initials: Y
authors.lastname: Tu
authors.forename: Randi
authors.initials: R
authors.lastname: Stern
authors.forename: Edward R
authors.initials: ER
authors.lastname: Garrity
authors.forename: Sangeeta M
authors.initials: SM
authors.lastname: Bhorade
authors.forename: Steven R
authors.initials: SR
authors.lastname: White
mesh_terms: D000328:Adult; D001989:Bronchiolitis Obliterans / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D016040:Lung Transplantation / Q000009:adverse effects*; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D016572:Cyclosporine