Local administration of epidermal growth factor receptor tyrosine kinase inhibitor may provide a new therapeutic potential for the treatment of intractable upper airway inflammation

• Takezawa Kumiko

  Department of Otorhinolaryngology, Shiga University of Medical Science

• Ogawa Takao

  Department of Otorhinolaryngology, Shiga University of Medical Science

• Shimizu Shino

  Department of Otorhinolaryngology, Shiga University of Medical Science

• Shimizu Takeshi

  Department of Otorhinolaryngology, Shiga University of Medical Science

Bibliographic Information

Other Title

• 難治性上気道炎症に対する新たな局所治療薬としてのEpidermal growth factor （EGF） 受容体阻害薬の可能性

Abstract

Eosinophilic chronic rhinosinusitis (ECRS) is a refractory upper airway disease, characterized by significant eosinophil infiltration, glue-like rhinorrhea and recurrent nasal polyposis. In our previous study, we found that epithelial cell-eosinophil interactions and thrombin generated by the activation of coagulation system, stimulated the production of MUC5AC mucin and profibrotic cytokines involved in the tissue remodeling such as goblet cell metaplasia and nasal polyp formation. These actions were mediated by epidermal growth factor receptor (EGFR) transactivation of the epithelial cells, and EGFR tyrosine kinase inhibitor significantly inhibited them. We then examined (1) in vitro effects of EGFR tyrosine kinase inhibitor AG1478 on LPS- or TNF-α induced secretion of MUC5AC mucin and IL-8, and (2) in vivo effects of AG1478 on LPS- or antigen-induced goblet cell metaplasia and neutrophil/eosinophil infiltration in rat nasal epithelium. AG1478 significantly inhibited LPS- or TNF-α induced secretion and mRNA expression of MUC5AC mucin and IL-8, and intraperitoneal injection of AG1478 inhibited LPS- or antigen-induced goblet cell metaplasia, mucus production and neutrophil/eosinophil infiltration in rat nasal epithelium. Intranasal instillation of AG1478 showed similar inhibitory effects on LPS-induced changes in rat nasal epithelium. The results indicate that local administration of EGFR inhibitor may provide a new therapeutic potential for the treatment of intractable airway diseases such as ECRS.

Journal

• Journal of Japan Society of Immunology & Allergology in Otolaryngology

  Journal of Japan Society of Immunology & Allergology in Otolaryngology 34 (1), 1-7, 2016

  JAPAN SOCIETY OF IMMUNOLOGY AND ALLERGOLOGY IN OTOLARYNGOLOGY

Keywords

• eosinophilic chronic rhinosinusitis
• epidermal growth factor receptor
• goblet cell metaplasia
• mucus hypersecretion

Details

• CRID: 1390001204352467712
• NII Article ID: 130005141309
• DOI: 10.5648/jjiao.34.1
• ISSN: 21855900
• ISSN: 09130691
• Web Site: https://www.jstage.jst.go.jp/article/jjiao/34/1/34_1/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016396188
• Text Lang: ja
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed