title: Hypoxia increases epithelial permeability in human nasal epithelia.
abstract: OBJECTIVE
  The nasal mucosa is the first site to encounter pathogens, and it forms continuous barriers to various stimuli. This barrier function is very important in the innate defense mechanism. Additionally, inflammation of the nasal sinus is known to be a hypoxic condition. Here, we studied the effect of hypoxia on barrier function in normal human nasal epithelial (NHNE) cells.
  
  
  METHODS
  The expression levels of various junction complex proteins were assessed in hypoxia-stimulated NHNE cells and human nasal mucosal tissues. We performed real-time polymerase chain reaction analysis, western blotting, and immunofluorescence assays to examine differences in the mRNA and protein expression of ZO-1, a tight junction protein, and E-cadherin in NHNE cells. Moreover, we evaluated the trans-epithelial resistance (TER) of NHNE cells under hypoxic conditions to check for changes in permeability. The expression of ZO-1 and E-cadherin was measured in human nasal mucosa samples by western blotting.
  
  
  RESULTS
  Hypoxia time-dependently decreased the expression of ZO-1 and E-cadherin at the gene and protein levels. In addition, hypoxia decreased the TER of NHNE cells, which indicates increased permeability. Human nasal mucosa samples, which are supposed to be hypoxic, showed significantly decreased levels of ZO-1 and E-cadherin expression compared with control.
  
  
  CONCLUSIONS
  Our results demonstrate that hypoxia altered the expression of junction complex molecules and increased epithelial permeability in human nasal epithelia. This suggests that hypoxia causes barrier dysfunction. Furthermore, it may be associated with innate immune dysfunction after encountering pathogens.
authors.affiliation: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.; The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Min
authors.affiliation: The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Korea.; Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.; The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Korea.; Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Joo-Heon
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.; The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Korea. ENTMAN@yuhs.ac.
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Kim
mesh_terms: D015153:Blotting, Western; D015820:Cadherins / Q000032:analysis* / Q000235:genetics; D004848:Epithelium / Q000737:chemistry / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000209:etiology / Q000378:metabolism*; D008565:Membrane Proteins / Q000032:analysis*; D009297:Nasal Mucosa / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology; D010539:Permeability / Q000528:radiation effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D019108:Tight Junctions / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein
chemical_list: D015820:Cadherins; D008565:Membrane Proteins; D012333:RNA, Messenger; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein
keywords: E-cadherin; Hypoxia; ZO-1; permeability
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