title: Budesonide and fluticasone propionate differentially affect the airway epithelial barrier.
abstract: BACKGROUND
  COPD patients have a higher risk of pneumonia when treated with fluticasone propionate (FP) than with placebo, and a lower risk with budesonide (BUD). We hypothesized that BUD and FP differentially affect the mucosal barrier in response to viral infection and/or cigarette smoke.
  
  
  METHODS
  We assessed protective effects of equivalent concentrations of BUD and FP on cytokine production and barrier function (electrical resistance) in human bronchial epithelial 16HBE cells and primary bronchial epithelial cells (PBECs) upon exposure to viral mimetic poly-(I:C) and/or cigarette smoke extract (CSE) or epidermal growth factor (EGF).
  
  
  RESULTS
  BUD and FP were equally effective in suppressing poly-(I:C)- and/or CSE-induced IL-8 secretion in 16HBE and PBECs. Poly-(I:C) substantially decreased electrical resistance in 16HBE cells and both BUD and FP fully counteracted this effect. However, FP hardly affected 16HBE barrier dysfunction induced by CSE with/without poly-(I:C), whereas BUD (16 nM) provided full protection, an effect likely mediated by affecting EGFR-downstream target GSK-3β. Similarly, BUD, but not FP, significantly improved CSE-induced barrier dysfunction in PBECs. Finally, BUD, but not FP, exerted a modest but significant protective effect against Streptococcus Pneumoniae-induced barrier dysfunction, and BUD, but not FP, prevented cellular adhesion and/or internalization of these bacteria induced by poly-(I:C) in 16HBE.
  
  
  CONCLUSIONS
  Collectively, both BUD and FP efficiently control epithelial pro-inflammatory responses and barrier function upon mimicry of viral infection. Of potential clinical relevance, BUD more effectively counteracted CSE-induced barrier dysfunction, reinforcing the epithelial barrier and potentially limiting access of pathogens upon smoking in vivo.
authors.affiliation: Department of Pathology & Medical Biology, Experimental Pulmonology and Inflammation Research, University of Groningen, University Medical Center Groningen,, Hanzeplein 1, NL-9713 GZ, Groningen, The Netherlands. h.i.heijink@umcg.nl.|Department of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. h.i.heijink@umcg.nl.|University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands. h.i.heijink@umcg.nl.
authors.forename: I H
authors.initials: IH
authors.lastname: Heijink
authors.affiliation: Department of Pathology & Medical Biology, Experimental Pulmonology and Inflammation Research, University of Groningen, University Medical Center Groningen,, Hanzeplein 1, NL-9713 GZ, Groningen, The Netherlands.
authors.forename: M R
authors.initials: MR
authors.lastname: Jonker
authors.affiliation: Department of Pathology & Medical Biology, Experimental Pulmonology and Inflammation Research, University of Groningen, University Medical Center Groningen,, Hanzeplein 1, NL-9713 GZ, Groningen, The Netherlands.|University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: de Vries
authors.affiliation: Department of Pathology & Medical Biology, Experimental Pulmonology and Inflammation Research, University of Groningen, University Medical Center Groningen,, Hanzeplein 1, NL-9713 GZ, Groningen, The Netherlands.|University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands.
authors.forename: A J M
authors.initials: AJ
authors.lastname: van Oosterhout
authors.affiliation: Department of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.|University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Telenga
authors.affiliation: Department of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.|University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands.
authors.forename: N H T
authors.initials: NH
authors.lastname: Ten Hacken
authors.affiliation: Department of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.|University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands.
authors.forename: D S
authors.initials: DS
authors.lastname: Postma
authors.affiliation: Department of Pulmonology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.|University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van den Berge
mesh_terms: D001980:Bronchi / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D001993:Bronchodilator Agents / Q000008:administration & dosage; D019819:Budesonide / Q000008:administration & dosage*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D000068298:Fluticasone / Q000008:administration & dosage*; D006801:Humans; D011066:Poly C / Q000276:immunology*; D012229:Rhinovirus / Q000187:drug effects / Q000502:physiology; D013638:Tars
chemical_list: D001993:Bronchodilator Agents; D016207:Cytokines; D013638:Tars; C024746:tobacco tar; D011066:Poly C; D019819:Budesonide; D000068298:Fluticasone