| Project/Area Number |
26860598
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Chiba University |
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Principal Investigator |
YOKOTA Masaya 千葉大学, 医学部附属病院, 助教 (70721950)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 気管支喘息 / 気道過敏性 / Muc5ac / IκBNS / 気道上皮細胞 / ステロイド / HDM |
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| Outline of Final Research Achievements |
To clarify the underlying mechanisms of refractory asthma, I aimed to determine the role of 11β-HSD2, which oxidizes cortisol to the inactive metabolite cortisone, in airway epithelial cells in asthma. I also aimed to determine the roles of IκBNS in allergic airway inflammation.
I found that HDM-induced airway inflammation was exacerbated but airway hyperresponsiveness (AHR) was attenuated in mice lacking IκBNS in non-hematopoietic cells. The induction of Muc5ac, a representative mucin in asthmatic airways, was reduced in IκBNS-deficient murine tracheal epithelial cells. Moreover, IκBNS bound to and activated Muc5ac distal promoter in epithelial cells. These results suggest that IκBNS is involved in the induction of AHR by inducing Muc5ac expression in lung epithelial cells and that IκBNS-Muc5ac axis in lung epithelial cells could be a therapeutic target for asthma. I am investigating the role of 11β-HSD2 in asthma by generating lung-specific 11β-HSD2-deficient mice.
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