title: Regulation of epithelial cell proliferation by bronchial fibroblasts obtained from mild asthmatic subjects.
abstract: BACKGROUND
  Bronchial epithelium is considered a key player in coordinating airway wall remodelling. The function of epithelial cells can be modulated by the underlying fibroblasts through autocrine and paracrine mechanisms.
  
  
  OBJECTIVE
  To investigate the effect of phenotypic changes in bronchial fibroblasts from asthmatic subjects on epithelial cell proliferation.
  
  
  METHODS
  Epithelial cells and fibroblasts derived from bronchial biopsies of asthmatic and healthy controls were cultured in an engineered model. Proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium-bromid (MTT). Epidermal growth factor receptor (EGFR), cyclin-dependent kinase inhibitors p21 and p27 were measured by western blots. Total and active forms of transforming growth factor (TGF)-β₁ were measured using ELISA and bioassay. TGF-β was inhibited using a recombinant TGF-β soluble receptor II protein.
  
  
  RESULTS
  Proliferation of epithelial cells from asthmatics (AE) is increased when cells were cultured with fibroblasts from normal controls (NF). Fibroblasts from asthmatics (AF) significantly decreased the proliferation of epithelial cells from healthy subjects (NE). Activation of p21, p27, EGFR and TGF-β₁ reflects the proliferation data by decreasing in AE cultured with NF and increasing in NE cultured with AF. Neutralization of TGF-β increased proliferation of epithelial cells cultured in the asthmatic model.
  
  
  CONCLUSIONS
  Fibroblasts from asthmatic subjects regulate epithelial cell prolifearation, and TGF-β signalling may represent one of the pathway involved in these interactions.
authors.affiliation: Centre de recherche, Institut universitaire de cardiologie et de pneumologie de Québec, Sainte-Foy, Québec, QC, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Semlali
authors.forename: E
authors.initials: E
authors.lastname: Jacques
authors.forename: M
authors.initials: M
authors.lastname: Rouabhia
authors.forename: J
authors.initials: J
authors.lastname: Milot
authors.forename: M
authors.initials: M
authors.lastname: Laviolette
authors.forename: J
authors.initials: J
authors.lastname: Chakir
mesh_terms: D001249:Asthma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D001980:Bronchi / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D066246:ErbB Receptors / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008855:Microscopy, Electron, Scanning; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D023822:Tissue Engineering; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology
chemical_list: D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016212:Transforming Growth Factor beta; D066246:ErbB Receptors