S1P and S1PR3 pathway has the role of eosinophilic airway inflammation via release of CCL20 from bronchial epithelial cell
| Project/Area Number |
16K19453
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
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| Research Collaborator |
NAGANO Tatsuya
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | スフィンゴ脂質 / スフィンゴシン1リン酸 / CCL20 / 上皮細胞 / 気管支喘息 / ALI / ARDS / S1P / 分子呼吸器内科学 / シグナル伝達 / 脂質 |
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| Outline of Final Research Achievements |
Sphingosine 1 phosphate (S1P) regulates diverse biological responses. The aim of this study is to reveal the relationship between S1P and S1P receptors (S1PR) using human bronchial epithelial cells and asthma mouse model. At first, transcriptome analysis was performed from total RNA of BEAS2B and Calu-3 cells stimulated with S1P. The expression of CCL 20 was evaluated with knockdown S1PRs. Then, the effect of anti-CCL20 antibody and VPC23019, S1PR1 and 3 antagonist, was examined in the ovalbumin (OVA)-induced bronchial asthma model.
Stimulation with S1P induced the expression of CCL20. Expression of CCL20 was highest in BEAS2B. The knockdown of S1PR3 reduced expression of CCL20. In the asthma mouse model, anti-CCL20 antibody and VPC23019 significantly reduced the number of eosinophils in bronchoalveolar lavage fluid. In conclusions, the S1P and S1PR3 pathway regulates the production of CCL20. Therefore, this pathway might have the potential to be a target for asthma treatment.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究から、スフィンゴシン1リン酸とその受容体3型の経路は、気道上皮細胞からのCCL20の産生に重要な役割を果たしていることが明らかとなった。気道上皮細胞は喘息の新しい治療標的として注目されており、今回の研究により気道上皮細胞を標的とする喘息の新しい分子標的治療薬の候補が発見できた。この治療薬はいまだ喘息患者の10人に1人存在するという難治性喘息患者の治療法として効果が期待される。
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Report
(4 results)
Research Products
(2 results)
