| Project/Area Number |
26461186
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
須田 隆文 浜松医科大学, 医学部, 教授 (30291397)
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| Research Collaborator |
MORI KAZUTAKA 浜松医科大学, 医学部, 大学院生
YAMANAKA KATSUMASA 浜松医科大学, 医学部, 大学院生
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 気管支喘息 / 気道炎症 / IL-17A / Toll like receptor / 炎症性サイトカイン / 自然免疫 / 獲得免疫 / 気道上皮細胞 / IL-17 / TLR3 / Toll-like receptor / polyI:C |
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| Outline of Final Research Achievements |
The interaction between IL-17A and TLR3 activation in airway epithelium remains poorly understood. In this study, we demonstrated that IL-17A and polyI:C, the ligand of TLR3, synergistically induced proinflammatory cytokine and chemokine (G-CSF, IL-8) mRNA and protein expression. Inhibition of the NF-κB pathway using NF-κB p65 siRNA, or BAY11-7082 (IκB-α inhibitor) attenuated the IL-17A/polyI:C-induced synergistic expression of proinflammatory cytokines. Knockdown of IRF3 using siRNA also decreased the synergistic gene expression. In western blotting analysis, co-treatment with IL-17A and polyI:C augmented IκB-α phosphorylation compared to polyI:C treatment alone. These findings demonstrate that IL-17A and TLR3 activation act in concert to potentiate proinflammatory responses in the airway epithelium via NF-κB/IRF3 activation, and that enhanced activation of the NF-κB pathway play a key role in the synergism.
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