Epidermal growth factor receptor signaling mediates regranulation of rat nasal goblet cells

Heung Man Lee, Lars Malm, Karim Dabbagh, Trang Dao-Pick, Iris F. Ueki, Suil Kim, Jae Jeong Shim, Jay A. Nadel

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Mucus hypersecretion is a common response to inflammation in the lower airways and is a hallmark of chronic rhinitis. Objective: The purpose of this study was to elucidate the mechanisms of regranulation (mucus production) of goblet cells in nasal epitheliumú Methods: Because neutrophils induce an epidermal growth factor (EGFR) cascade, we induced degranulation of goblet cells in rat nasal respiratory epithelium by means of intranasal inhalation of N-formyl-methionyl-leucyl-phenylalanine (fMLP), and we examined regranulation of the goblet cells and the role of EGFR inhibitors and neutrophils in the regranulation process. Results: In the control state Alcian blue/periodic acid-Schiff and mucin MUC5AC staining was present. Degranulation was induced in the nasal septal epithelium 4 hours after intranasal inhalation of fMLP (10-7 mol/L); 48 hours later, goblet-cell regranulation was complete. In the control state EGFR protein staining was absent in the epithelium, but after fMLP-induced degranulation, EGFR protein was expressed. After pretreatment with BIBX1522, a selective EGFR tyrosine kinase inhibitor, fMLP-induced degranulation was unaffected, but goblet-cell regranulation was prevented completely. Conclusion: These data suggest a role for the EGFR cascade in neutrophil-dependent production of goblet-cell mucins. Proving this theory will require the use of selective EGFR inhibitors in clinical studies of nasal hypersecretory states.

Original languageEnglish
Pages (from-to)1046-1050
Number of pages5
JournalJournal of Allergy and Clinical Immunology
Volume107
Issue number6
DOIs
Publication statusPublished - 2001
Externally publishedYes

Keywords

  • Epidermal growth factor receptor cascade
  • Epidermal growth factor receptor tyrosine kinase activation
  • Mucin expression
  • Nasal hypersecretion
  • Secretory cell growth

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Lee, H. M., Malm, L., Dabbagh, K., Dao-Pick, T., Ueki, I. F., Kim, S., Shim, J. J., & Nadel, J. A. (2001). Epidermal growth factor receptor signaling mediates regranulation of rat nasal goblet cells. Journal of Allergy and Clinical Immunology, 107(6), 1046-1050. https://doi.org/10.1067/mai.2001.115140