Innovation of drug seeds against B7-H1 involved in exacerbation of obstructive lung diseases

• Project/Area Number: 15K09222
• 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, 医学研究院, 准教授 (60325462)
• Co-Investigator(Kenkyū-buntansha): 福山 聡 九州大学, 大学病院, 講師 (50380530)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: B7-H1 / PD-L1 / 気管支喘息 / COPD / ウィルス感染 / 複合病態

Outline of Final Research Achievements

Airway viral infections cause the exacerbations of obstructive lung diseases. B7-H1/PD-L1 is an immune-checkpoint molecule that plays a role in an escape mechanism of viruses from the host immune systems. This escape may be associated with the persistence of viral infection and the exacerbation of the underlying diseases. In a study in vitro, we have shown that a PI3-kinase-delta inhibitor attenuated the upregulation of B7-H1/PD-L1 on airway epithelial cells stimulated with an analog of viral double-stranded(ds) RNA. In this study, we investigated the effect of PI3-kinase inhibitor on the expression of B7-H1/PD-L1 in dsRNA-induced inflammation in mice. Administration of dsRNA upregulated the expression of B7-H1/PD-L1 and induced neutrophilic inflammation, which were suppressed by pretreatment with the PI3-kinase inhibitor. These results suggest PI3-kinase-delta inhibitor as a candidate of clinical use for preventing the virus-induced exacerbations of obstructive lung diseases.

Research Products

• [Journal Article] Effects of corticosteroid plus long-acting beta2-agonist on the expression of PD-L1 in double-stranded RNA-induced lung inflammation in mice. (2017)
  • Author(s): Hamano S, Matsumoto K, Tonai K, Fukuyama S, Kan-o K, Seki N, Inoue H, Nakanishi Y
  • Journal Title: Journal of Inflammation Volume: 14 Issue: 1 Pages: 2-2
  • DOI: 10.1186/s12950-017-0149-4
  • Peer Reviewed / Open Access
• [Journal Article] Interleukin-22 attenuates double-stranded RNA-induced upregulation of PD-L1 in airway epithelial cells via a STAT3-dependent mechanism. (2017)
  • Author(s): Seki N, Kan-o K, Matsumoto K, Fukuyama S, Hamano S, Tonai K, Ota K, Inoue H, Nakanishi Y
  • Journal Title: Biochemical Biophysical Research Communications Volume: 94 Issue: 1-2 Pages: 242-248
  • DOI: 10.1016/j.bbrc.2017.10.045
  • Peer Reviewed
• [Journal Article] Effects of corticosteroid plus long-acting beta2-agonist on the expression of PD-L1 in double-stranded RNA-induced lung inflammation in mice. (2017)
  • Author(s): Hamano S, Matsumoto K, Tonai K, Fukuyama S, Kan-o K, Seki N, Inoue H, Nakanishi Y.
  • Journal Title: The Journal of Inflammation Volume: 14
  • Peer Reviewed / Open Access / Acknowledgement Compliant