IL-13 induces mucin production by stimulating epidermal growth factor receptors and by activating neutrophils

Jae Jeong Shim, Karim Dabbagh, Iris F. Ueki, Trang Dao-Pick, Pierre Regis Burgel, Kiyoshi Takeyama, Dominic Cheng Wei Tam, Jay A. Nadel

Research output: Contribution to journalArticlepeer-review

213 Citations (Scopus)

Abstract

Mucus hypersecretion contributes to the morbidity and mortality in acute asthma. Both T helper 2 (Th2) cytokines and epidermal growth factor receptor (EGFR) signaling have been implicated in allergen-induced goblet cell (GC) metaplasia. Present results show that a cascade of EGFR involving neutrophils is implicated in interleukin (IL)-13-induced mucin expression in GC. Treatment with a selective EGFR tyrosine kinase inhibitor prevented IL-13-induced GC metaplasia dose dependently and completely. Instillation of IL-13 also induced tumor necrosis factor-α protein expression, mainly in infiltrating neutrophils. Control airway epithelium contained few leukocytes, but intratracheal instillation of IL-13 resulted in time-dependent leukocyte recruitment by IL-13-induced IL-8-like chemoattractant expression in airway epithelium. Pretreatment with an inhibitor of leukocytes in the bone marrow (cyclophosphamide) or with a blocking antibody to IL-8 prevented both IL-13-induced leukocyte recruitment and GC metaplasia. These findings indicate that EGFR signaling is involved in IL-13-induced mucin production. They suggest a potential therapeutic role for inhibitors of the EGFR cascade in the hypersecretion that occurs in acute asthma.

Original languageEnglish
Pages (from-to)L134-L140
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume280
Issue number1 24-1
Publication statusPublished - 2001 Jan
Externally publishedYes

Keywords

  • Airway epithelium
  • Epidermal growth factor receptor activation
  • Interleukin
  • Mucus hypersecretion
  • T helper 2 cytokine

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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