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 language | English |
|---|---|
| Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
| Volume | 280 |
| Issue number | 1 24-1 |
| Publication status | Published - 2001 Jan 1 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - IL-13 induces mucin production by stimulating epidermal growth factor receptors and by activating neutrophils
AU - Shim, Jae Jeong
AU - Dabbagh, Karim
AU - Ueki, Iris F.
AU - Dao-Pick, Trang
AU - Burgel, Pierre Regis
AU - Takeyama, Kiyoshi
AU - Tam, Dominic Cheng Wei
AU - Nadel, Jay A.
PY - 2001/1/1
Y1 - 2001/1/1
N2 - 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.
AB - 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.
KW - Airway epithelium
KW - Epidermal growth factor receptor activation
KW - Interleukin
KW - Mucus hypersecretion
KW - T helper 2 cytokine
UR - http://www.scopus.com/inward/record.url?scp=0035009330&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035009330&partnerID=8YFLogxK
M3 - Article
C2 - 11133503
AN - SCOPUS:0035009330
VL - 280
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
SN - 1040-0605
IS - 1 24-1
ER -