title: Cigarette smoke exposure impairs respiratory epithelial ciliogenesis.
abstract: BACKGROUND
  Cigarette smoke exposure is considered an important negative prognostic factor for chronic rhinosinusitis (CRS) patients. However, there is no clear mechanistic evidence implicating cigarette smoke exposure in the poor clinical evolution of the disease or in the maintenance of the inflammatory state characterizing CRS. This study aimed to evaluate the effects of cigarette smoke exposure on respiratory cilia differentiation.
  
  
  METHODS
  Mouse nasal septal epithelium cultures grown at an air-liquid interface were used as a model of respiratory epithelium. After 5 days of cell growth, cultures were exposed to air on the apical surface. Additionally, cigarette smoke condensate (CSC; the particulate phase of tobacco smoke) or cigarette smoke extract (CSE; the volatile phase) were diluted in the basolateral compartment in different concentrations. After 15 days of continuous exposure, scanning electron microscopy and immunofluorescence for type IV tubulin were used to determine presence and maturation of cilia. Transepithelial resistance was also recorded to evaluate confluence and physiological barrier integrity.
  
  
  RESULTS
  CSC and CSE impair ciliogenesis in a dose-dependent manner with notable effects in concentrations higher than 30 microg/mL, yielding >70% nonciliation and shorter cilia compared with control. No statistical difference on transepithelial resistance was evident.
  
  
  CONCLUSIONS
  CSC and CSE exposure negatively impacts ciliogenesis of respiratory cells at concentrations not effecting transepithelial resistance. The impairment on ciliogenesis reduces the mucociliary clearance apparatus after injury and/or infection and may explain the poor response to therapy for CRS patients exposed to tobacco smoke.
authors.affiliation: Department of Ophthalmology, Otorhinolaryngology, and Head and Neck Surgery, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
authors.forename: Edwin
authors.initials: E
authors.lastname: Tamashiro
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Xiong
authors.forename: Wilma T
authors.initials: WT
authors.lastname: Anselmo-Lima
authors.forename: James L
authors.initials: JL
authors.lastname: Kreindler
authors.forename: James N
authors.initials: JN
authors.lastname: Palmer
authors.forename: Noam A
authors.initials: NA
authors.lastname: Cohen
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002908:Chronic Disease; D002923:Cilia / Q000378:metabolism* / Q000473:pathology; D004781:Environmental Exposure / Q000009:adverse effects*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D012220:Rhinitis / Q000209:etiology / Q000503:physiopathology; D012307:Risk Factors; D012852:Sinusitis / Q000209:etiology / Q000503:physiopathology; D012907:Smoking / Q000009:adverse effects*; D014404:Tubulin / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D014404:Tubulin