Immunomodulatory role of PGD2/CRTH2 pathway in the pathophysiology of refractory lung diseases

• Project/Area Number: 21590971
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Keio University
• Principal Investigator: ASANO Koichiro 慶應義塾大学, 医学部, 准教授 (60192944)
• Co-Investigator(Kenkyū-buntansha): FUKUNAGA Koichi 慶應義塾大学, 医学部, 助教 (60327517) ; OGUMA Tsuyoshi 慶應義塾大学, 医学部, 講師 (20255441)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 気管支喘息 / 肺線維症 / 敗血症 / CRTH2 / 好中球 / プロスタグランジン / 喘息

Research Abstract

Previous studies by us and other researchers have clarified the role of PGD2 receptor, CRTH2, on allergic diseases including asthma by the activities on eosinophils and Th2 lymphocytes. In the present study, we have demonstrated that PGD2/CRTH2 pathway plays an essential role in the pathophysiology of chronic asthma, pulmonary fibrosis, and sepsis by modulating gamma-delta T cells and neutrophils.

Research Products

• [Journal Article] CRTH2 Is A Critical Regulator of Neutrophil Migration and Resistance to Polymicrobial Sepsis (2012)
  • Author(s): M. Ishii, K. Asano, H. Namkoong, S. Tasaka, K. Mizoguchi, T. Asami, H. Kamata, Y. Kimizuka, H. Fujiwara, Y. Funatsu, S. Kagawa, J. Miyata, K. Ishii, M. Nakamura, H. Hirai, K. Nagata, S. L. Kunkel, N. Hasegawa, and T. Betsuyaku
  • Journal Title: J Immunol Volume: (in press)
  • Peer Reviewed
• [Journal Article] Role of prostaglandin D2 receptor, CRTH2, in sustained eosinophil accumulation in the airways of mice with chronic asthma (2011)
  • Author(s): S. Kagawa, K. Fukunaga, Y. Shiraishi, T. Oguma, Y. Suzuki, T. Shiomi, K. Sayama, N. Kimura, H. Hirai, K. Nagata, M. Nakamura, K. Asano
  • Journal Title: Int Arch Allergy Immunol Volume: 155 Pages: 6-11
  • Peer Reviewed
• [Journal Article] Induction of mucin and MUC5AC expression by the protease activity of Aspergillus fumigatus in airway epithelial cells (2011)
  • Author(s): T. Oguma, K. Asano, K. Tomomatsu, M. Kodama, K. Fukunaga, T. Shiomi, N. Ohmori, S. Ueda, T. Takihara, Y. Shiraishi, K. Sayama, S. Kagawa, Y. Natori, C. M. Lilly, K. Satoh, K. Makimura, and A. Ishizaka
  • Journal Title: J Immunol Volume: 187(2) Pages: 999-1005
  • Peer Reviewed
• [Journal Article] 「脂質メディエーター最前線」抗炎症性脂質メディエーター (2011)
  • Author(s): 宮田純、福永興壱、浅野浩一郎
  • Journal Title: 喘息 Volume: 24(2) Pages: 164-171
• [Journal Article] CRTH2 is a critical regulator for neutrophil migration and resistance to poly microbial sepsis (2011)
  • Author(s): M Ishii, K Asano, et al
  • Journal Title: J Immunol Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Induction of mucin and MUC5AC expression by the protease activity of Aspergillus fumigatus in airway epithelial cells (2011)
  • Author(s): T.Oguma, K.Asano, et al
  • Journal Title: J Immunol Volume: 187 Issue: 2 Pages: 999-1005
  • DOI: 10.4049/jimmunol.1002257
  • Peer Reviewed
• [Journal Article] 「アレルギー疾患と脂質メディエーター」プロスタグランジンD2と受容体 (2010)
  • Author(s): 浅野浩一郎
  • Journal Title: 臨床免疫・アレルギー科 Volume: 54(1) Pages: 44-50
• [Journal Article] Strain-specific phenotypes of airway inflammation and bronchial hyperresponsiveness induced by epicutaneous allergen sensitisation in BALB/c and C57BL/6 mice (2010)
  • Author(s): M.Kodama, K.Asano, et al.
  • Journal Title: Int Arch Allergy Immunol Volume: 152 Pages: 67-74
  • Peer Reviewed
• [Journal Article] The anti-inflammatory and pro-resolving mediator Resolvin E1 protects mice from bacterial pneumonia and acute lung injury (2010)
  • Author(s): H.Seki, K.Asano, et al.
  • Journal Title: J Immunol 184 Pages: 836-843
  • Peer Reviewed
• [Journal Article] Strain-specific phenotypes of airway inflammation and bronchial hyperresponsiveness induced by epicutaneous allergen sensitisation in BALB/c and C57BL/6 mice (2010)
  • Author(s): M.Kodama, K.Asano, et al.
  • Journal Title: Int Arch Allergy Immunol 152(印刷中)
  • Peer Reviewed
• [Journal Article] Glucocorticoid protects rodent hearts from ischemia/reperfusion injury by activating lipocalin-type prostaglandin D synthase-derived PGD2 biosynthesis (2009)
  • Author(s): S. Tokudome, M. Sano, K. Shinmura, T. Matsuhashi, S. Morizane, H. Moriyama, K. Tamaki, K. Hayashida, H. Nakanishi, N. Yoshikawa, N. Shimizu, J. Endo, T. Katayama, M. Murata, S. Yuwasa, R. Kaneda, K. Tomita, N. Eguchi, Y. Urade, K. Asano, Y. Utsunomiya, T.Suzuki, R. Taguchi, H. Tanaka, and K. Fukuda
  • Journal Title: J Clin Invest Volume: 119 Pages: 1477-1488
  • Peer Reviewed
• [Presentation] Prostaglandin D2 receptor, CRTH2, is critical for gamma-delta T cell-mediated suppression of pulmonary inflammation/fibrosis induced by bleomycin (2011)
  • Author(s): K Asano, S Ueda, M Ishii, Y Suzuki, K Fukunaga, T Oguma, M Nakamura, K Nagata, H Hirai
  • Organizer: 12th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases
  • Place of Presentation: Seattle, USA
  • Year and Date: 2011-09-20
• [Presentation] Prostaglandin D_2 receptor, CRTH2, is critical for gamma-delta T cell-mediated suppression of pulmonary inflammation/fibrosis induced by bleomycin (2011)
  • Author(s): K Asano, S Ueda, M Ishii, Y Suzuki, K Fukunaga, T Oguma, M Nakamura, K Nagata, H Hirai
  • Organizer: ATS 2011 International Conference
  • Place of Presentation: Denver, USA
  • Year and Date: 2011-05-18
• [Presentation] Critical Roles of prostaglandin D_2 receptor CRTH2 in a mice model of poly microbial sepsis (2011)
  • Author(s): M Ishii, N Hasegawa, K Asano, et al
  • Organizer: ATS 2011 International Conference
  • Place of Presentation: Denver, USA
  • Year and Date: 2011-05-18
• [Presentation] Critical Roles of prostaglandin D_2 receptor CRTH2 in a mice model of polymicrobial sepsis (2011)
  • Author(s): M Ishii, N Hasegawa, K Mizoguchi, H Namkoong, S Kagawa, M Nakamura, H Hirai, K Nagata, S Tasaka, K Asano
  • Organizer: ATS 2011 International Conference
  • Place of Presentation: Denver, USA
  • Year and Date: 2011-05-17
• [Presentation] Prostaglandin D2 receptor, CRTH2, is critical for gamma-delta T cell-mediated suppression of pulmonary inflammation/fibrosis induced by bleomycin (2011)
  • Author(s): K Asano, S Ueda, M Ishii, et al
  • Organizer: ATS 2011 International Conference
  • Place of Presentation: Denver, USA
  • Year and Date: 2011-05-17
• [Presentation] Asano Prostaglandin D_2 receptor CRTH2 is a critical regulator in a mice model of polymicrobial sepsis (2011)
  • Author(s): M Ishii, N Hasegawa, H Namkoong, S Kagawa, M Nakamura, H Hirai, K Nagata, S Tasaka K
  • Organizer: 第51回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2011-04-22
• [Presentation] PGD2受容体CRTH2を介する肺臓炎・線維化抑制の分子機序 (2011)
  • Author(s): 上田壮一郎, 浅野浩一郎, 加川志津子, 田中希布人、滝原崇久, 福永興壱, 小熊剛, 佐山宏一
  • Organizer: 第51回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2011-04-22
• [Presentation] 慢性喘息モデルにおけるプロスタグランジンD_2(PGD_2)受容体CRTH2の意義 (2010)
  • Author(s): 加川志津子、浅野浩一郎、福永興壱、樹神元博、小川里佳、友松克允、小倉裕美、宮田純、田中希宇人、上石修史、加畑宏樹、塩見哲也、小熊剛、佐山宏一
  • Organizer: 第60回日本アレルギー学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-11-25
• [Presentation] 抗原反復暴露による慢性好酸球性気道炎症におけるプロスタグランジンD_2(PGD_2)受容体CRTH2の意義 (2010)
  • Author(s): 加川志津子、浅野浩一郎、白石良樹、福永興壱、樹神元博、大森奈緒、友松克允、小倉裕美、宮田純、田中希宇人、上石修史、塩見哲也、小熊剛、佐山宏一
  • Organizer: アレルギー好酸球研究会2010
  • Place of Presentation: 東京
  • Year and Date: 2010-06-19
• [Presentation] 敗血症におけるプロスタグランジンD2とその受容体CRTH2の役割に関する検討 (2010)
  • Author(s): 石井誠、長谷川直樹、田坂定智、浅野浩一郎
  • Organizer: 第25回日本ショック学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-29
• [Presentation] ワークショップ「アレルギー疾患と脂質メディエーター-最近の知見-」プロスタグランジンD_2と受容体 (2009)
  • Author(s): 浅野浩一郎、上田壮一郎、白石良樹、加川志津子、福永興壱、石坂彰敏
  • Organizer: 第59回日本アレルギー学会秋期学術大会
  • Place of Presentation: 秋田
  • Year and Date: 2009-10-31
• [Presentation] プロスタグランジンD_2と受容体 (2009)
  • Author(s): 浅野浩一郎
  • Organizer: 第59回日本アレルギー学会秋期学術大会
  • Place of Presentation: 秋田
  • Year and Date: 2009-10-31
• [Presentation] プロスタグランジンD_2受容体CRTH2を介したブレオマイシン肺臓炎の炎症制御機構 (2009)
  • Author(s): 上田壮一郎, 浅野浩一郎, 加川志津子, 田中希布人、滝原崇久, 福永興壱, 小熊剛, 佐山宏一, 石坂彰敏
  • Organizer: 第12回間質性肺炎分子病態研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-08-22
• [Presentation] プロスタグランジンD_2受容体CRTH2を介したブレオマイシン肺臓炎の病態修飾 (2009)
  • Author(s): 上田壮一郎, 浅野浩一郎, 白石良樹, 加川志津子, 滝原崇久, 中島剛, 福永興壱, 小熊剛, 佐山宏一, 石坂彰敏
  • Organizer: 第49回日本呼吸器学会総会
  • Place of Presentation: 東京
  • Year and Date: 2009-06-12
• [Presentation] Role of PGD2 and its receptors in respiratory diseases (2009)
  • Author(s): K Asano
  • Organizer: 4^<th> International Conference on Phsopholipase A2 and Lipid Mediators
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2009-06-12