Epigenetic regulation during lethal post-influenza pneumococcal infection
Project/Area Number |
17H07090
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Single-year Grants |
Research Field |
Respiratory organ internal medicine
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Research Institution | Keio University |
Principal Investigator |
Yagi Kazuma 慶應義塾大学, 医学部(信濃町), 助教 (00594566)
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Project Period (FY) |
2017-08-25 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | インフルエンザ感染後肺炎球菌2次感染 / エピジェネティクス / Ezh2コンディショナルノックアウトマウス / エピジェネティック制御機構 |
Outline of Final Research Achievements |
Secondary bacterial pneumonia following influenza virus infection is associated with high mortality, but the mechanism is largely unknown. We established mouse model of secondary bacterial pneumonia following influenza virus infection. Mice were infected intranasally with Streptococcus pneumoniae, 7 days after intranasal inoculation with influenza virus. We hypothesized that epigenetic gene regulation via histone methylation was involved in the pathogenesis of lethal postinfluenza bacterial pneumonia. The survival rate of Ezh2 cKO mice was significantly decreased after post-influenza pneumococcal pneumonia. Lung NK cells were significantly higher in Ezh2 cKO mice after pneumococcal infection, and the survival rate of Ezh2 cKO mice was improved by administering NK cell neutralizing antibody. These results suggest that Ezh2 might have protective effect via regulation of NK cell-related genes in the mouse model of post-influenza pneumococcal infection.
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Academic Significance and Societal Importance of the Research Achievements |
インフルエンザウイルス感染に続発する肺炎球菌2次感染は致死的であり病態は十分に明らかになっておらず、抗菌薬や抗ウイルス薬による治療のみでの予後改善が難しいという現状がある。本研究では、同疾患においてエピジェネティクス(DNAの配列変化を伴わない遺伝子発現を制御・伝達する機構)という新しい角度からのアプローチを試み、NK細胞という免疫担当細胞がその病態に関与している可能性を見出した。将来的な新規薬剤の創薬や予後改善につながる一助になると考えられる。
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Report
(3 results)
Research Products
(11 results)
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[Journal Article] Association between six-minute walk test parameters and the health-related quality of life in patients with pulmonary Mycobacterium avium complex disease.2018
Author(s)
Yagi K, Asakura T, Namkoong H, Suzuki S, Asami T, Okamori S, Kusumoto T, Funatsu Y, Kamata H, Nishimura T, Ishii M, Betsuyaku T, Hasegawa N.
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Journal Title
BMC Pulm Med.
Volume: 18(1)
Issue: 1
Pages: 114-121
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clarithromycin expands CD11b+Gr-1+ cells via the STAT3/Bv8 axis to ameliorate lethal endotoxic shock and post-influenza bacterial pneumonia.2018
Author(s)
Namkoong H1,2, Ishii M1, Fujii H3, Yagi K1, Asami T1, Asakura T1, Suzuki S1, Hegab AE1, Kamata H1, Tasaka S1, Atarashi K4, Nakamoto N5, Iwata S6,7, Honda K4, Kanai T5, Hasegawa N6, Koyasu S4,8, Betsuyaku T1.
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Journal Title
PLOS Pathogens
Volume: 14(4)
Issue: 4
Pages: e1006955-e1006955
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Sphingosine 1-phosphate receptor modulator ONO-4641 stimulates CD11b+Gr-1+ cell expansion and inhibits lymphocyte infiltration in the lungs to ameliorate murine pulmonary emphysema.2018
Author(s)
Asakura T, Ishii M, Namkoong H, Suzuki S, Kagawa S, Yagi K, Komiya T, Hashimoto T, Okamori S, Kamata H, Tasaka S, Kihara A, Hegab AE, Hasegawa N, Betsuyaku T. S
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Journal Title
Mucosal Immunol.
Volume: 11(6)
Issue: 6
Pages: 1606-1620
DOI
Related Report
Peer Reviewed
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[Journal Article] Clinical characteristics of pulmonary Mycobacterium lentiflavum disease in adult patients.2018
Author(s)
Yagi K, Morimoto K, Ishii M, Namkoong H, Okamori S, Asakura T, Suzuki S, Asami T, Uwamino Y, Funatsu Y, Fujiwara H, Kamata H, Nishimura T, Betsuyaku T, Kurashima A, Hasegawa N.
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Journal Title
International Journal of Infectious Diseases
Volume: 67
Pages: 65-69
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The efficacy, safety, and feasibility of inhaled amikacin for the treatment of difficult-to-treat non-tuberculous mycobacterial lung diseases.2017
Author(s)
Yagi K, Ishii M, Namkoong H, Asami T, Iketani O, Asakura T, Suzuki S, Sugiura H, Yamada Y, Nishimura T, Fujiwara H, Funatsu Y, Uwamino Y, Kamo T, Tasaka S, Betsuyaku T, Hasegawa N
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Journal Title
BMC Infectious Diseases
Volume: 17(1)
Issue: 1
Pages: 558-558
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Impact of chronic Pseudomonas aeruginosa infection on health-related quality of life in Mycobacterium avium complex lung disease.2017
Author(s)
Kamata H1, Asakura T1,2, Suzuki S1,2, Namkoong H1, Yagi K1, Funatsu Y1, Okamori S1, Uno S3, Uwamino Y4, Fujiwara H3, Nishimura T5, Ishii M1, Betsuyaku T1, Hasegawa N6.
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Journal Title
BMC Pulmonary Medicine
Volume: 17(1)
Issue: 1
Pages: 198-198
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Impact of Cavity and Infiltration on Pulmonary Function and Health-Related Quality of Life in Mycobacterium avium complex Pulmonary Disease: A 3-Dimensional Computed Tomographic Analysis2017
Author(s)
Asakura T, Yamada Y, Namkoong H, Suzuki S, Niijima Y, Kamata H, Funatsu Y, Yagi K, Okamori S, Sugiura H, Ishii M, Jinzaki M, Betsuyaku T, Hasegawa N
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Journal Title
Respir Med
Volume: 126
Pages: 9-16
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Impact of six-minute walk test on health-related quality of life in pulmonary Mycobacterium avium complex disease2018
Author(s)
Yagi K, Asakura T, Namkoong H, Suzuki S, Asami T, Okamori S, Kusumoto T, Funatsu Y, Kamata H, Nishimura T, Ishii M, Betsuyaku T, Hasegawa N.
Organizer
European Respiratory Society (ERS) International Congress 2018
Related Report
Int'l Joint Research
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[Presentation] The efficacy, safety and feasibility of inhaled amikacin for the treatment of refractory non-tuberculous mycobacterial lung diseases.2017
Author(s)
Kazuma Yagi, Makoto Ishii, Ho Namkoong, Takahiro Asami, Osamu Iketani, Takanori Asakura, Shoji Suzuki, Satoshi Okamori, Hiroaki Sugiura, Yoshitake Yamada, Tomoyasu Nishimura, Hirofumi Kamata, Hiroshi Fujiwara, Yohei Funatsu, Yoshifumi Uwamino, Tomoko Betsuyaku, Naoki Hasegawa.
Organizer
ERS International Congress 2017
Related Report
Int'l Joint Research