난알부민을 이용한 알레르기 비염 모델에서 상피성장인자 수용체 Tyrosine Kinase 억제제가 배세포 형성에 미치는 영향

초록

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.

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