title: The Impact of Pepsin on Human Nasal Epithelial Cells In Vitro: A Potential Mechanism for Extraesophageal Reflux Induced Chronic Rhinosinusitis.
abstract: OBJECTIVE
  To describe potential mechanisms by which pepsin induces inflammation in refractive chronic rhinosinusitis (CRS). Our hypothesis was that pepsin induces mitochondrial damage and cytokine expression in human nasal epithelial cells (HNEpC) in vitro.
  
  
  METHODS
  Western blot was used to detect pepsin in sinus lavages from patients with CRS and controls. The HNEpC cells were treated with pepsin (pH 7; 0.1 mg/mL) for 1 or 16 hours and routine electron microscopy (EM) and MTT assay were performed. Cytokine ELISA was performed on media collected from HNEpC cells 16 hours following a 1-hour pepsin treatment.
  
  
  RESULTS
  Pepsin was detected in sinus lavages from 4 out of 6 CRS patients and 0 out of 3 controls. The EM showed mitochondrial damage in pepsin-treated HNEpC cells but not in control cells. The MTT assay demonstrated reduced mitochondrial activity in pepsin-treated HNEpC cells compared to controls (P < .001). Pepsin increased IL-1A (P = .003) and IL-6 (P = .04) expression in HNEpC cells.
  
  
  CONCLUSIONS
  Pepsin in sinus lavages from patients with CRS is consistent with previous studies. This study reveals the damaging effect of pepsin on mitochondria in nasal epithelial cells in vitro. Cytokines previously associated with CRS were elevated following pepsin treatment of HNEpC cells in vitro. These results demonstrate mechanisms by which pepsin may potentiate CRS.
authors.affiliation: Division of Rhinology and Sinus Surgery, Department of Otolaryngology & Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Southwood
authors.affiliation: Division of Rhinology and Sinus Surgery, Department of Otolaryngology & Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Hoekzema
authors.affiliation: Division of Rhinology and Sinus Surgery, Department of Otolaryngology & Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Tina L
authors.initials: TL
authors.lastname: Samuels
authors.affiliation: Division of Rhinology and Sinus Surgery, Department of Otolaryngology & Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Clive
authors.initials: C
authors.lastname: Wells
authors.affiliation: Division of Rhinology and Sinus Surgery, Department of Otolaryngology & Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Poetker
authors.affiliation: Division of Rhinology and Sinus Surgery, Department of Otolaryngology & Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Nikki
authors.initials: N
authors.lastname: Johnston
authors.affiliation: Division of Rhinology and Sinus Surgery, Department of Otolaryngology & Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA tloehrl@mcw.edu.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Loehrl
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D002478:Cells, Cultured; D002908:Chronic Disease; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D017817:Nasal Lavage Fluid; D009297:Nasal Mucosa / Q000166:cytology*; D010434:Pepsin A / Q000494:pharmacology*; D012220:Rhinitis / Q000473:pathology; D012852:Sinusitis / Q000473:pathology
chemical_list: D005765:Gastrointestinal Agents; D053582:Interleukin-1alpha; D015850:Interleukin-6; D010434:Pepsin A
keywords: chronic rhinosinusitis; extraesophageal reflux; mucosal immunology; pepsin; reflux; sinusitis