Potential use of an anticancer drug gefinitib, an EGFR inhibitor, on allergic airway inflammation
- Authors
- Hur, Gyu Young; Lee, Sung Yong; Lee, Seung Hyeun; Kim, Se Joong; Lee, Kyoung Ju; Jung, Jin Yong; Lee, Eun Joo; Kang, Eun Hae; Jung, Ki Hwan; Lee, Sang Yeub; Kim, Je Hyeong; Shin, Choi; Shim, Jae Jeong; In, Kwang Ho; Kang, Kyung Ho; Yoo, Se Hwa
- Issue Date
- 30-Jun-2007
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- asthma; gefitinib; mucins; 1-phosphatidylinositol 3-kinase; proto-oncogene proteins c-akt; receptor, epidermal growth factor
- Citation
- EXPERIMENTAL AND MOLECULAR MEDICINE, v.39, no.3, pp 367 - 375
- Pages
- 9
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- EXPERIMENTAL AND MOLECULAR MEDICINE
- Volume
- 39
- Number
- 3
- Start Page
- 367
- End Page
- 375
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/17890
- DOI
- 10.1038/emm.2007.41
- ISSN
- 1226-3613
2092-6413
- 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 (Pl3K)/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.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 2. Clinical Science > Department of Pulmonary, Allergy, and Critical Care Medicine > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.