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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2007.1
- 수록면
- 367 - 375 (9page)
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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.
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참고문헌 (26)
참고문헌 신청
Amishima M / 1998 / Expression of epidermal growth factor and epidermal growth factor receptor immunoreactivity in the asthmatic human airway 157 : 1907 ~ 1912
Andrianifahanana M / 2006 / Regulation of mucin expression: Mechanistic aspects and implications for cancer and inflammatory diseases 1765 : 189 ~ 222
Bogdan S / 2001 / Epidermal growth factor receptor signaling 11 : R292 ~ R295
Burgel PR / 2004 / Roles of epidermal growth factor re-ceptor activation in epithelial cell repair and mucin production in airway epithelium 59 : 992 ~ 996
Cantley LC / 2002 / The phosphoinositide 3-kinase pathway 296 : 1655 ~ 1657
Andrianifahanana M / 2006 / Regulation of mucin expression: Mechanistic aspects and implications for cancer and inflammatory diseases 1765 : 189 ~ 222
Bogdan S / 2001 / Epidermal growth factor receptor signaling 11 : R292 ~ R295
Burgel PR / 2004 / Roles of epidermal growth factor re-ceptor activation in epithelial cell repair and mucin production in airway epithelium 59 : 992 ~ 996
Cantley LC / 2002 / The phosphoinositide 3-kinase pathway 296 : 1655 ~ 1657
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