Inhibition of COPD development by inhibiting chemokine receptor CCR4 function.
| Project/Area Number |
21K20857
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0902:General internal medicine and related fields
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| Research Institution | Yamagata University |
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Principal Investigator |
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| Project Period (FY) |
2021-08-30 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 慢性閉塞性肺疾患 / CC chemokine ligand 17 / CC chemokine receptor 4 / 肺気腫 / マクロファージ / CCR4 / CCL17 |
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| Outline of Research at the Start |
慢性閉塞性肺疾患(COPD)は世界的に患者や死亡者も多い健康上の脅威であるが、根本的な治療法が確立されていない。我々のこれまでの研究でCOPDの病態進行にCCL17/TARCというケモカインが関与していることが示された。本研究ではCCL17/TARCとその受容体であるCCR4に着目し、これらの機能がCOPDの病態進展にどのように関係しているかを検討する研究を計画した。本研究によりCOPDの病態を解明し、新規治療法の解明に結びつくことが期待される。
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| Outline of Final Research Achievements |
Chemokine receptor CCR4 knockout mice were exposed to cigarette smoking for 2 days. Bronchoalveolar lavage (BAL) was performed and cell counts and fractions were assessed. Even though control mice showed an increase in total cell counts and macrophage fractions in the BAL after smoking exposure, this increase was significantly suppressed in the knockout mice.
In addition, these mice were exposed to cigarette smoking to 6 months, and a histological examination was performed. The results showed that the mean linear intercept, a quantitative measure of pulmonary emphysema, was significantly reduced in knockout mice, indicating that emphysema formation in the lung was suppressed in the absence of CCR4 in mice.
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| Academic Significance and Societal Importance of the Research Achievements |
慢性閉塞性肺疾患（COPD）は世界の死因の上位を占め、呼吸機能低下による身体活動の低下は健康寿命を損なう大きな原因となる重要な疾患である。COPDは主に喫煙を原因として発症するが、喫煙者の一部にのみ発症するため何らかの喫煙感受性の存在が指摘されている。本研究により喫煙による肺組織の炎症や肺気腫形成にCCR4が関わっていることを示し、本因子がCOPD発症の病態形成に大きな役割を持つ可能性があることを示唆した。現在COPDの発症を予防したり根治したりする方法は存在しないため、本研究は将来COPDの治療や発症予防に対し、創薬を期待することができる大変意義深いものである。
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Report
(3 results)
Research Products
(5 results)
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[Journal Article] Role of CC Chemokine Ligand 17 in Mouse Models of Chronic Obstructive Pulmonary Disease2022
Author(s)
Machida Hiroyoshi、Inoue Sumito、Igarashi Akira、Saitoh Shinichi、Yamauchi Keiko、Nishiwaki Michiko、Nemoto Takako、Otaki Yoichiro、Sato Masamichi、Sato Kento、Nakano Hiroshi、Yang Sujeong、Furuyama Kodai、Murano Hiroaki、Ishibashi Yu、Ota Takahito、Nakayama Takashi、Shibata Yoko、Watanabe Masafumi
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Journal Title
American Journal of Respiratory Cell and Molecular Biology
Volume: 66
Issue: 4
Pages: 428-438
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effect of hyperhomocysteinemia on a murine model of smoke-induced pulmonary emphysema.2022
Author(s)
Nakano H, Inoue S, Minegishi Y, Igarashi A, Tokairin Y, Yamauchi K, Kimura T, Nishiwaki M, Nemoto T, Otaki Y, Sato M, Sato K, Machida H, Yang S, Murano H, Watanabe M, and Shibata Y.
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Journal Title
Scientific Reports
Volume: 12
Issue: 1
Pages: 12968-12968
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The Incidence and Risk Analysis of Lung Cancer Development in Patients with Chronic Obstructive Pulmonary Disease: Possible Effectiveness of Annual CT-Screening.2021
Author(s)
Machida H, Inoue S, Shibata Y, Kimura T, Ota T, Ishibashi Y, Murano H, Furuyama K, Yang S, Nakano H, Sato K, Sato M, Nemoto T, Nishiwaki M, Yamauchi K, Igarashi A, Watanabe M.
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Journal Title
Int J Chron Obstruct Pulmon Dis.
Volume: 16
Pages: 739-749
DOI
Related Report
Peer Reviewed / Open Access
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