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

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

Research output: Contribution to journalArticle

37 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
Publication statusPublished - 2007 Jun 30

Fingerprint

Ovalbumin
Inflammation
Eosinophils
Pharmaceutical Preparations
Interleukin-13
Bronchoalveolar Lavage Fluid
Interleukin-4
Protein-Tyrosine Kinases
Phosphotransferases
Epithelium
Cell Count
Cytokines
Lung
Phosphorylation
Goblet Cells
Fluids
Mucus
Hyperplasia
Asthma
Chemical activation

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Genetics

Cite this

Potential use of an anticancer drug gefinitib, an EGFR inhibitor, on allergic airway inflammation. / Hur, Gyu Young; Lee, Sung Yong; Lee, Seung Heon; Se, Joong Kim; Kyoung, Ju Lee; Jin, Yong Jung; Lee, Eun Joo; Eun, Hae Kang; Ki, Hwan Jung; Lee, Sang Yeub; Kim, Je Hyeong; Shin, Chol; Shim, Jae Jeong; In, Kwang Ho; Kyung, Ho Kang; Se, Hwa Yoo.

In: Experimental and Molecular Medicine, Vol. 39, No. 3, 30.06.2007, p. 367-375.

Research output: Contribution to journalArticle

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