Korean J Otolaryngol-Head Neck Surg.  2001 Apr;44(4):376-380.

Effect of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor on the Goblet Cell Production in Ovalbumin-sensitized Rats

• Lee HM
• Hwang SJ
• Lee SH

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

Ovalbumin; Allergic rhinitis; MUC5AC; Epidermal; growth factor receptor

MeSH Terms

Animals
Epidermal Growth Factor*
Goblet Cells*
Hypersensitivity
In Situ Hybridization
Inflammation
Models, Animal
Mucins
Mucus
Nasal Mucosa
Ovalbumin
Ovum
Phosphotransferases
Protein-Tyrosine Kinases
Rats*
Rats, Inbred F344
Receptor, Epidermal Growth Factor*
RNA, Messenger
Epidermal Growth Factor
Mucins
Ovalbumin
Phosphotransferases
Protein-Tyrosine Kinases
RNA, Messenger
Receptor, Epidermal Growth Factor