Oncostatin M promotes mucosal epithelial barrier dysfunction, and its expression is increased in patients with eosinophilic mucosal disease

Kathryn L. Pothoven, James E. Norton, Kathryn E. Hulse, Lydia A. Suh, Roderick G. Carter, Erin Rocci, Kathleen E. Harris, Stephanie Shintani-Smith, David B. Conley, Rakesh K. Chandra, Mark C. Liu, Atsushi Kato, Nirmala Gonsalves, Leslie C. Grammer, Anju T. Peters, Robert C. Kern, Paul J. Bryce, Bruce K. Tan, Robert P. Schleimer*

*Corresponding author for this work

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)737-746.e4
JournalJournal of Allergy and Clinical Immunology
Volume136
Issue number3
DOIs
StatePublished - Sep 1 2015

Fingerprint

Oncostatin M
Epithelial Cells
Eosinophilic Esophagitis
Nasal Polyps
Bronchoalveolar Lavage Fluid
Electric Impedance
Nose
Nasal Lavage Fluid
Air
Macroglobulins
Tissue Extracts
Tight Junctions
Allergens
Fluorescent Antibody Technique
Cultured Cells
Asthma
Color
Biopsy

Keywords

  • Oncostatin M
  • atopic asthma
  • chronic rhinosinusitis
  • eosinophilic esophagitis
  • epithelial barrier
  • tight junctions
  • transepithelial electrical resistance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

@article{cada7d71218d4b48a82d2b26149b618e,
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.",
keywords = "Oncostatin M, atopic asthma, chronic rhinosinusitis, eosinophilic esophagitis, epithelial barrier, tight junctions, transepithelial electrical resistance",
author = "Pothoven, {Kathryn L.} and Norton, {James E.} and Hulse, {Kathryn E.} and Suh, {Lydia A.} and Carter, {Roderick G.} and Erin Rocci and Harris, {Kathleen E.} and Stephanie Shintani-Smith and Conley, {David B.} and Chandra, {Rakesh K.} and Liu, {Mark C.} and Atsushi Kato and Nirmala Gonsalves and Grammer, {Leslie C.} and Peters, {Anju T.} and Kern, {Robert C.} and Bryce, {Paul J.} and Tan, {Bruce K.} and Schleimer, {Robert P.}",
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language = "English (US)",
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Oncostatin M promotes mucosal epithelial barrier dysfunction, and its expression is increased in patients with eosinophilic mucosal disease. / Pothoven, Kathryn L.; Norton, James E.; Hulse, Kathryn E.; Suh, Lydia A.; Carter, Roderick G.; Rocci, Erin; Harris, Kathleen E.; Shintani-Smith, Stephanie; Conley, David B.; Chandra, Rakesh K.; Liu, Mark C.; Kato, Atsushi; Gonsalves, Nirmala; Grammer, Leslie C.; Peters, Anju T.; Kern, Robert C.; Bryce, Paul J.; Tan, Bruce K.; Schleimer, Robert P.

In: Journal of Allergy and Clinical Immunology, Vol. 136, No. 3, 01.09.2015, p. 737-746.e4.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Oncostatin M promotes mucosal epithelial barrier dysfunction, and its expression is increased in patients with eosinophilic mucosal disease

AU - Pothoven, Kathryn L.

AU - Norton, James E.

AU - Hulse, Kathryn E.

AU - Suh, Lydia A.

AU - Carter, Roderick G.

AU - Rocci, Erin

AU - Harris, Kathleen E.

AU - Shintani-Smith, Stephanie

AU - Conley, David B.

AU - Chandra, Rakesh K.

AU - Liu, Mark C.

AU - Kato, Atsushi

AU - Gonsalves, Nirmala

AU - Grammer, Leslie C.

AU - Peters, Anju T.

AU - Kern, Robert C.

AU - Bryce, Paul J.

AU - Tan, Bruce K.

AU - Schleimer, Robert P.

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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.

KW - Oncostatin M

KW - atopic asthma

KW - chronic rhinosinusitis

KW - eosinophilic esophagitis

KW - epithelial barrier

KW - tight junctions

KW - transepithelial electrical resistance

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DO - 10.1016/j.jaci.2015.01.043

M3 - Article

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JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

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