Potential use of an anticancer drug gefinitib, an EGFR inhibitor, on allergic airway inflammation

Young Hur Gyu, Yong Lee Sung, Hyeun Lee Seung, Joong Kim Se, Ju Lee Kyoung, Yong Jung Jin, Joo Lee Eun, Hae Kang Eun, Hwan Jung Ki, Yeub Lee Sang, Hyeong Kim Je, Chol Shin, Jeong Shim Jae, Ho In Kwang, Ho Kang Kyung, Hwa Yoo Se

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The EGFR plays an essential role in goblet cell hyperplasia and mucus hypersecretion. EGFR has an intrinsic tyrosine kinase activity that, when activated, induces the production of MUC5AC through the signaling kinase cascade in the airway epithelium. We have investigated the effects of an EGFR tyrosine kinase inhibitor, gefitinib, on ovalbumin (OVA)-induced, allergic inflammation in airway epithelia of mice. OVA-sensitized mice were pretreated with gefitinib at two different doses (12.5 and 50 mg/kg) and then challenged with OVA. The OVA challenge increased the total cell count and eosinophil count in bronchoalveolar lavage fluid (BALF), as well as the concentrations of T-helper2 (Th2) cytokines, such as IL-4 and IL-13, overall eosinophil recruitment in the lung tissue and airway hyperresponsiveness (AHR). Pretreatment with gefitinib reduced the inflammatory cell counts and released cytokine concentrations (IL-4 and IL-13) in BALF, as well as eosinophil recruitment in the lungs and AHR, in a dose-dependent manner. This was associated with decreased EGFR and Akt phosphorylation. We showed that gefitnib inhibits EGFR and phosphoinositol 3′-kinase (PI3K)/Akt activation which were activated in OVA sensitized mice. These findings suggest that inhibitors of the EGFR cascade may have a role in the treatment of asthma.

Original languageEnglish
Pages (from-to)367-375
Number of pages9
JournalExperimental and Molecular Medicine
Volume39
Issue number3
DOIs
Publication statusPublished - 2007 Jun 30

Keywords

  • 1-phosphatidylinositol 3-kinase
  • Asthma
  • Gefitinib
  • Mucins
  • Proto-oncogene proteins c-akt
  • Receptor, epidermal growth factor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

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  • Cite this

    Gyu, Y. H., Sung, Y. L., Seung, H. L., Se, J. K., Kyoung, J. L., Jin, Y. J., Eun, J. L., Eun, H. K., Ki, H. J., Sang, Y. L., Je, H. K., Shin, C., Jae, J. S., Kwang, H. I., Kyung, H. K., & Se, H. Y. (2007). Potential use of an anticancer drug gefinitib, an EGFR inhibitor, on allergic airway inflammation. Experimental and Molecular Medicine, 39(3), 367-375. https://doi.org/10.1038/emm.2007.41