Effect of epithelial mesenchymal transition on innate immune responses by airway epithelial cells
| Project/Area Number |
17K09633
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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 | Tokyo National Hospital (Clinical research) |
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Principal Investigator |
Ohshima Nobuharu 独立行政法人国立病院機構東京病院(臨床研究部), 臨床研究部, アレルギー科医長 (10724023)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | EMT / 喘息 / 気道上皮細胞 / サイトカイン / 上皮間葉転換 / 上皮間葉転換 (EMT) / TGF-β1 / A549細胞 / CpG ODN / タバコ抽出液 / NFκB / MAPキナーゼ / LPS / SREC-1 / アレルギー・ぜんそく / 自然免疫 |
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| Outline of Final Research Achievements |
Epithelial-mesenchymal transition (EMT) is reported to be one of the mechanisms involved in induction of airway remodeling in severe asthma. The present study was performed to clarify the role of EMT caused by by airway epithelial cells in the innate immune response. EMT-induced A549 cells by TGF-β1 showed significantly greater production of inflammatory cytokines in response to LPS stimuli via SREC-1 as a receptor. On the other hand, those cells showed significantly greater production of inflammatory cytokines in response to CpG stimuli through activation of NFκB. In conclusion, upon induction of EMT, airway epithelial cells showed a stronger immune response against pathogens in terms of inflammatory cytokine production, which may be a cause of acute exacerbation of asthma in patients with a respiratory tract infection.
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| Academic Significance and Societal Importance of the Research Achievements |
重症喘息では気道リモデリングを伴うことが多く、またしばしば呼吸器感染症に伴う急性増悪によりQOLが大きく妨げられる。本研究では、気道リモデリングの原因の一つである気道上皮細胞のEMTにより、外来微生物由来抗原に対するサイトカイン・ケモカイン産生応答が亢進することで、病態がより重篤化する可能性が示唆された。喘息のみならず、EMTが関与すると考えられている間質性肺炎や肺癌においても、呼吸器感染症による急性増悪に同様の機序が関与している可能性も推察され、本研究結果を用いてその機序を明らかにし、治療ターゲットまで解明することが期待される。
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] Epithelial-mesenchymal transition of human lung adenocarcinoma A549 cells up-regulates cytokine production upon LPS stimulation.2017
Author(s)
Kato T, Kobayashi K, Suzukawa M, Saito M, Okuda K, Koyama K, Igarashi S, Arakawa S, Ohshima N, Matsui H, Nagase T, Ohta K
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Journal Title
Allergology International
Volume: 66S
Pages: 56-58
NAID
Related Report
Peer Reviewed
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