Pharmacological regulation of B7-H1 expression for treating COPD and asthma exacerbation

• Project/Area Number: 24591132
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kyushu University
• Principal Investigator: MATSUMOTO Koichiro 九州大学, 大学病院, 講師 (60325462)
• Co-Investigator(Kenkyū-buntansha): FUKUYAMA Satoru 九州大学, 大学病院, 助教 (50380530)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: COPD / 気管支喘息 / B7-H1 / PD-L1 / 低分子化合物 / ウィルス感染 / 2本鎖RNA / poly IC / virus / PI3 kinase delta / mouse / 国際情報交換

Outline of Final Research Achievements

Airway viral infection leads to exacerbation of COPD and asthma. B7-H1(PD-L1) is induced on virus-infected cells and works as an inhibitor of anti-viral defence. The elucidation of induction mechanisms is expected to dampen persistent infection. In an experimental model in which B7-H1 is induced by a synthetic analogue of viral double-stranded RNA, poly IC, or respiratory syncytial virus on human airway epithelial cells, we showed that virus-related induction of B7-H1 depends on the activation of PI3 kinase, a representative kinase in cell proliferation and maintaining of cell survival. Additionally, we have developped in vivo experimental model that airway inflammation with B7-H1 upregulation is induced by intra-tracheal administration of poly IC in mice. Treatment of mice with a PI3 kinase inhibitor tended to attenuate the poly IC-induced upregulation of B7-H1. These results suggest that PI3 kinase may be a therapeutic target of virus-induced pathgenesis of chronic airway diseases.

Research Products

• [Journal Article] PI3K-delta mediates double-stranded RNA-induced upregulation of B7-H1 in BEAS-2B airway epithelial cells. (2013)
  • Author(s): Keiko Kan-o, Koichiro Matsumoto, Asai-Tajiri Yukari, Satoru Fukuyama, Saaka Hamano, Nanae Seki, Yoichi Nakanishi, Hiromasa Inoue
  • Journal Title: Biochemical Biophysical Research Communications Volume: 435 Pages: 195-201
  • Peer Reviewed
• [Presentation] PI3K-delta mediates double-stranded RNA-induced upregulation of B7-H1 on airway epithelialium (2013)
  • Author(s): Koichiro Matsumoto
  • Organizer: Annual meeting of American Association of Immunology
  • Place of Presentation: Honolulu, USA
• [Presentation] PI3 kinase-delta mediates double-stranded RNA-induced upregulation on airway epithlium (2013)
  • Author(s): Koichiro Matsumoto（松元幸一郎）
  • Organizer: Annual meeting of American Association of Immunology
  • Place of Presentation: Honolulu, USA