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KMID : 0361020010440040376
Korean Journal of Otolaryngology - Head and Neck Surgery
2001 Volume.44 No. 4 p.376 ~ p.380
Effect of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor on the Goblet Cell Production in Ovalbumin-sensitized Rats
ÀÌÈ︸/Heung Man Lee
Ȳ¼øÀç/ÀÌ»óÇÐ/Soon Jae Hwang/Sang Hag Lee
Abstract
Background and Objectives : Hypertrophic and metaplastic changes of goblet cells associated with mucus hypersecretion are common characteristics of airway inflammation. The purposes of this study were to observe goblet cell production in an
allergic
animal model and to elucidate the effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor on goblet cell production. Materials and methods : We produced used ovalbumin (OVA)-sensitized F344 rats as an animal model of nasal
allergy.
Rats were sensitized and challenged with OVA (OVA-sensitized rats). Control rats were given saline alone. Nasal mucosa was processed for AB(pH2.5)/PAS stain, for immunohistochemical staining with anti-EGFR antibody, and for in situ hybridization
with
MUC5AC mucin gene. The effects of EGFR tyrosine kinase activation on OVA-induced goblet cell production were also examined. Results : Intraepithelial mucosubstance in the nasal mucosa increased significantly at 48h following OVA instillation in
the
OVA-sensitized rats. Immunohistochemical studies with an anti-EGFR antibody showed EGFR staining selectively in cells that stained positively with AB/PAS. In situ hybridization analysis demonstrated the expression of MUC5AC mRNA in
OVA-sensitized
rats,
but not in the control rats. Pretreatment with a selective EGFR kinase inhibitor (BIBX1522, 80 mg/kg/d, i.p.) inhibited OVA-induced goblet cell production. Conclusions: These results indicate that EGFR tyrosine kinase activation may play an
important
role in antigen-induced mucus production.
KEYWORD
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