title: Oncostatin M promotes mucosal epithelial barrier dysfunction, and its expression is increased in patients with eosinophilic mucosal disease.
abstract: BACKGROUND
  Epithelial barrier dysfunction is thought to play a role in many mucosal diseases, including asthma, chronic rhinosinusitis (CRS), and eosinophilic esophagitis.
  
  
  OBJECTIVE
  The objective of this study was to investigate the role of oncostatin M (OSM) in epithelial barrier dysfunction in human mucosal disease.
  
  
  METHODS
  OSM expression was measured in tissue extracts, nasal secretions, and bronchoalveolar lavage fluid. The effects of OSM stimulation on barrier function of normal human bronchial epithelial cells and nasal epithelial cells cultured at the air-liquid interface were assessed by using transepithelial electrical resistance and fluorescein isothiocyanate-dextran flux. Dual-color immunofluorescence was used to evaluate the integrity of tight junction structures in cultured epithelial cells.
  
  
  RESULTS
  Analysis of samples from patients with CRS showed that OSM mRNA and protein levels were highly increased in nasal polyps compared with those seen in control uncinate tissue (P < .05). OSM levels were also increased in bronchoalveolar lavage fluid of allergic asthmatic patients after segmental allergen challenge and in esophageal biopsy specimens from patients with eosinophilic esophagitis. OSM stimulation of air-liquid interface cultures resulted in reduced barrier function, as measured by decreased transepithelial electrical resistance and increased fluorescein isothiocyanate-dextran flux (P < .05). Alterations in barrier function by OSM were reversible, and the viability of epithelial cells was unaffected. OSM levels in lysates of nasal polyps and uncinate tissue positively correlated with levels of α2-macroglobulin, a marker of epithelial leak, in localized nasal secretions (r = 0.4855, P < .05).
  
  
  CONCLUSIONS
  These results suggest that OSM might play a role in epithelial barrier dysfunction in patients with CRS and other mucosal diseases.
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Pothoven
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: James E
authors.initials: JE
authors.lastname: Norton
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Hulse
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Lydia A
authors.initials: LA
authors.lastname: Suh
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Roderick G
authors.initials: RG
authors.lastname: Carter
authors.affiliation: Stritch School of Medicine, Loyola University Chicago, Chicago, Ill.
authors.forename: Erin
authors.initials: E
authors.lastname: Rocci
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Harris
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Shintani-Smith
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: David B
authors.initials: DB
authors.lastname: Conley
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Chandra
authors.affiliation: Divisions of Allergy and Clinical Immunology, Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, Md.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Liu
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Nirmala
authors.initials: N
authors.lastname: Gonsalves
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Grammer
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Anju T
authors.initials: AT
authors.lastname: Peters
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kern
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bryce
authors.affiliation: Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Tan
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill; Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, Ill. Electronic address: rpschleimer@northwestern.edu.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Schleimer
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D016022:Case-Control Studies; D002908:Chronic Disease; D003911:Dextrans / Q000378:metabolism; D057765:Eosinophilic Esophagitis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009298:Nasal Polyps / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053683:Oncostatin M / Q000235:genetics* / Q000276:immunology; D010539:Permeability; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics* / Q000276:immunology; D012220:Rhinitis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012852:Sinusitis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019108:Tight Junctions / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D003911:Dextrans; C508351:OSM protein, human; D012333:RNA, Messenger; C015219:fluorescein isothiocyanate dextran; D053683:Oncostatin M; D016650:Fluorescein-5-isothiocyanate
keywords: Oncostatin M; atopic asthma; chronic rhinosinusitis; eosinophilic esophagitis; epithelial barrier; tight junctions; transepithelial electrical resistance
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