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 journalArticle

206 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
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume280
Issue number1 24-1
Publication statusPublished - 2001 Jan 1
Externally publishedYes

Fingerprint

Interleukin-13
Mucins
Neutrophils
Epidermal Growth Factor Receptor
Goblet Cells
Metaplasia
Leukocytes
Interleukin-8
Asthma
Epithelium
Blocking Antibodies
Airway Management
Chemotactic Factors
Mucus
ErbB Receptors
Protein-Tyrosine Kinases
Allergens
Cyclophosphamide
Tumor Necrosis Factor-alpha
Bone Marrow

Keywords

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

ASJC Scopus subject areas

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

Cite this

IL-13 induces mucin production by stimulating epidermal growth factor receptors and by activating neutrophils. / Shim, Jae Jeong; Dabbagh, Karim; Ueki, Iris F.; Dao-Pick, Trang; Burgel, Pierre Regis; Takeyama, Kiyoshi; Tam, Dominic Cheng Wei; Nadel, Jay A.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 280, No. 1 24-1, 01.01.2001.

Research output: Contribution to journalArticle

Shim, Jae Jeong ; Dabbagh, Karim ; Ueki, Iris F. ; Dao-Pick, Trang ; Burgel, Pierre Regis ; Takeyama, Kiyoshi ; Tam, Dominic Cheng Wei ; Nadel, Jay A. / IL-13 induces mucin production by stimulating epidermal growth factor receptors and by activating neutrophils. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2001 ; Vol. 280, No. 1 24-1.
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