2013 Fiscal Year Final Research Report
Altering the Th1/Th2/Th17 balance as a therapeutic option for refractory asthma
Project/Area Number |
23591112
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
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Research Institution | University of Tsukuba |
Principal Investigator |
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Project Period (FY) |
2011 – 2013
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Keywords | 難治性喘息 / ステロイド抵抗性 / 好中球 / Th2細胞 / Th17細胞 / GATA-3 / RORγt / IL-6 |
Research Abstract |
GATA-3-overexpressing mice exhibited steroid-sensitive eosinophilic inflammation under Th2-biased conditions and RORgammat-overexpressing mice developed steroid-insensitive neutrophilic inflammation under Th17-biased conditions. The levels of KC, MIP-2, IL-6 and other neutrophil chemotaxis-related mediators were significantly elevated in OVA-exposed RORgammat-overexpressing mice, compared with wild-type mice. Interestingly, airway hyperresponsiveness accompanied by neutrophilic airway inflammation in RORgammat-overexpressing mice was effectively suppressed by anti-IL-17 antibody, CXCR2 antagonist or anti-IL-6 receptor antibody administration. In conclusion, our results suggest that the expression levels of GATA-3 and RORgammat may be important for determining the phenotype of asthmatic airway inflammation. Furthermore, blockade of the Th17 signaling pathway may be a treatment option for steroid-insensitive asthma.
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[Presentation] Anti-IL-6 receptor antibody attenuates neutrophilic airway inflammation in RORγt-overexpressing mice2013
Author(s)
Ano S, Morishima Y, Ishii Y, Kaneko Y, Fujita J, Ohtsuka S, Matsuyama M, Nakazawa K, Ohta K, Matsuno Y, Kawaguchi M, Sakamoto T, Hizawa N.
Organizer
2013 International Conference of American Thoracic Society
Place of Presentation
Pennsylvania Convention Center, Philadelphia, USA
Year and Date
2013-05-21
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[Presentation] Th2/Th17 milieu determines the phenotype of airway inflammation in mice2012
Author(s)
Ano S, Morishima Y, Ishii Y, Yamadori T, Masuko H, Kaneko Y, Fujita J, Ohtsuka S, Matsuyama M, Nozato K, Kawaguchi M, Sakamoto T, Hizawa N.
Organizer
2012 International Conference of American Thoracic Society
Place of Presentation
Moscone Center, San Francisco, USA
Year and Date
2012-05-20
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