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

Research output: Contribution to journalArticle

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

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Pothoven, K. L., Norton, J. E., Hulse, K. E., Suh, L. A., Carter, R. G., Rocci, E., Harris, K. E., Shintani-Smith, S., Conley, D. B., Chandra, R. K., Liu, M. C., Kato, A., Gonsalves, N., Grammer, L. C., Peters, A. T., Kern, R. C., Bryce, P. J., Tan, B. K., & Schleimer, R. P. (2015). Oncostatin M promotes mucosal epithelial barrier dysfunction, and its expression is increased in patients with eosinophilic mucosal disease. Journal of Allergy and Clinical Immunology, 136(3), 737-746.e4. https://doi.org/10.1016/j.jaci.2015.01.043