Involvement of a novel cytokine IL-17F in airway remodeling

2011 Fiscal Year Final Research Report

• Project/Area Number: 20790697
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: University of Tsukuba
• Principal Investigator: KAWAGUCHI Mio 筑波大学, 大学院・人間総合科学研究科, 講師 (50365748)
• Co-Investigator(Renkei-kenkyūsha): HIZAWA Nobuyuki 筑波大学, 大学院・人間総合科学研究科, 教授 (00301896) ; KOKUBU Fumio 昭和大学, 藤が丘病院呼吸器内科, 准教授 (21390254) ; MATSUKURA Satoshi 昭和大学, 呼吸器アレルギー内科, 講師 (10384231)
• Project Period (FY): 2008 – 2011
• Keywords: 気管支喘息 / IL-17F / 気道リモデリング

Research Abstract

We discovered IL-17F gene in 2001, and have reported its function in asthma. However, the role of IL-17F in asthma has not been fully elucidated. Although inhaled corticosteroids are the most potent medicines for long-term control of asthma, anti-asthma medicines including inhaled corticosteroids are generally not so effective for severe asthma. To this end, treating sever asthma is future serious problem in the world. Airway remodeling is deeply involved in the pathogenesis of severe asthma. Airway remodeling is caused by, at least partially, a complicated network of cytokines, including IL-11 and insulin-like growth factor-I (IGF-I). To clarify the pathogenesis of airway remodeling in asthma, we investigated the induction of IL-11 and IGF-I by IL-17F in bronchial epithelial cells. IL-17F is able to induce IL-11 and IGF-I via Raf1-MEK1/2-ERK1/2-MSK1/p90RSK-CREB signaling pathway in bronchial epithelial cells. Hence, the IL-17F/IGF-I axis may be involved in airway inflammation and remodeling. Therefore, IL-17F and its signaling pathway may be a valuable therapeutic target for sever asthma.

Research Products

• [Journal Article] Induction of insulin-likegrowth factor-I by interleukin-17F in bronchial epithelial cells (2010)
  • Author(s): Kawaguchi M, Fujita J, Kokubu F, Ohara G, Huang SK, Matsukura S, Ishii Y, Adachi M, Satoh H, Hizawa N
  • Journal Title: Clin Exp Allergy Volume: 40 Pages: 1036-1043
  • Peer Reviewed
• [Journal Article] IL-17F-induced IL-11 release in bronchial epithelial cells via MSK1-CREB pathway (2009)
  • Author(s): Kawaguchi M, Fujita J, Kokubu F, Huang SK, Homma T, Matsukura S, Adachi M, Hizawa N
  • Journal Title: Am JPhysiol Lung Cell Mol Physiol Volume: 296 Pages: L804-810
  • Peer Reviewed
• [Journal Article] Role of interleukin-17F in asthma (2009)
  • Author(s): Kawaguchi M, Kokubu F, Fujita J, Huang SK, Hizawa N
  • Journal Title: Inflamm. Allergy Drug Targets Volume: 8 Pages: 383-389
  • Peer Reviewed
• [Presentation] Induction ofIL-11 and IGF-I by IL-17F in bronchial epithelial cells (2010)
  • Author(s): 藤田純一, 川口未央, 國分二三男, 松倉聡, 増子裕典, 大原元, 阿野哲士, 山鳥忠宏, 谷下田雄一, 森島祐子, 石井幸雄, Shau-ku Hunag, 坂本透, 足立満, 檜澤伸之
  • Organizer: 106th International Conference of American Thoracic Society
  • Place of Presentation: 米国(ニューオーリンズ)
  • Year and Date: 2010-05-16
• [Presentation] IL-17Fによる気道上皮細胞からのIL-11の誘導 (2009)
  • Author(s): 藤田純一, 川口未央, 國分二三男, 松倉聡, 森島祐子, 石井幸雄, 坂本透, 足立満, 檜澤伸之
  • Organizer: 第17回臨床喘息研究会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-03
• [Presentation] IL-17F による気道上皮細胞からのIL-11の誘導 (2009)
  • Author(s): 藤田純一, 川口未央, 國分二三男, 松倉聡, 森島祐子, 石井幸雄, 坂本透, 足立満, 檜澤伸之
  • Organizer: 第19回国際喘息学会
  • Place of Presentation: 東京
  • Year and Date: 2009-07-05
• [Presentation] IL-17Fの新たなシグナル伝達経路:MSK1-CREB (2009)
  • Author(s): 藤田純一, 川口未央, 國分二三男, 松倉聡, 森島祐子, 石井幸雄, 坂本透, 足立満, 檜澤伸之
  • Organizer: 日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2009-06-13
• [Presentation] アレルギーとIL-17・Th17細胞臨床領域から (2009)
  • Author(s): 川口未央
  • Organizer: 日本アレルギー学会春季臨床大会
  • Place of Presentation: 岐阜
  • Year and Date: 2009-06-04
• [Presentation] IL-17Fのシグナル伝達経路:MSK1-CREBの関与 (2009)
  • Author(s): 藤田純一, 川口未央, 國分二三男, 松倉聡, 森島祐子, 石井幸雄, 坂本透, 足立満, 檜澤伸之
  • Organizer: 日本アレルギー学会春季臨床大会
  • Place of Presentation: 岐阜
  • Year and Date: 2009-06-04
• [Presentation] IL-17F induces IL-11 inbronchial epithelial cells (2009)
  • Author(s): 藤田純一, 川口未央, 國分二三男, 本間哲也, 鈴木慎太郎, 松倉聡, 森島祐子, 石井幸雄, Shau-ku Hunag, 足立満, 檜澤伸之
  • Organizer: 105thInternational Conference of American Thoracic Society
  • Place of Presentation: 米国 (サンディエゴ)
  • Year and Date: 2009-05-18
• [Presentation] IL-17Fの役割 (2008)
  • Author(s): 川口未央
  • Organizer: 16^<th> Symposium of Asthma in Tokyo
  • Place of Presentation: 東京
  • Year and Date: 2008-12-20
• [Presentation] IL-17Fによる気道上皮細胞からのIL-11とIGF-Iの発現 (2008)
  • Author(s): 藤田純一, 川口未央, 國分二三男, 本間哲也, 松倉聡, 森島祐子, 石井幸雄, 坂本透, 足立満, 檜澤伸之
  • Organizer: 第12回アレルギー・気道上皮細胞研究会
  • Place of Presentation: 東京
  • Year and Date: 2008-12-06
• [Presentation] 気管支喘息におけるIL-17Fの臨床的意義 (2008)
  • Author(s): 川口未央
  • Organizer: 第5回北関東信越呼吸器フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2008-07-05
• [Presentation] A new cytokine, IL-17F induces IGF-I in bronchial epithelial cells (2008)
  • Author(s): 川口未央, 國分二三男, 本間哲也, 尾高美保, 鈴木慎太郎, 渡辺伸, 松倉聡, 黒川真嗣, Shau-ku Hunag, 足立満
  • Organizer: 104th American Thoracic Society International Conference
  • Place of Presentation: カナダ(トロント)
  • Year and Date: 2008-05-13