Potential use of an anticancer drug gefinitib, an EGFR inhibitor, on allergic airway inflammation |
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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 Chol Shim Jae Jeong In Kwang Ho Kang Kyung Ho Yoo Se Hwa |
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Affiliation: | Department of Internal Medicine, College of Medicine, Korea University, Seoul 152-703, Korea. |
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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 gefinitib 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. |
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