九州大学 研究者情報
研究者情報 (研究者の方へ)入力に際してお困りですか?
基本情報 研究活動 教育活動 社会活動 病院臨床活動
松元 幸一郎(まつもと こういちろう) データ更新日:2019.06.26

准教授 /  医学研究院 附属胸部疾患研究施設 九州大学大学院医学研究院附属胸部疾患研究施設


主な研究テーマ
呼吸器ウィルス感染の機序の解明
キーワード:呼吸器、ウィルス、免疫
2019.06~2019.06.
閉塞性呼吸器疾患(慢性閉塞性肺疾患、気管支喘息など)における諸病態の解明と治療法の探索
キーワード:慢性閉塞性肺疾患、気管支喘息
2013.06~2019.12.
気管支喘息や慢性閉塞性肺疾患などの呼吸器疾患に関する基礎的・臨床的・疫学的研究
キーワード:気管支喘息、慢性閉塞性肺疾患、臨床肺機能、免疫学的機序
2000.07~2011.12.
従事しているプロジェクト研究
COPDに関する啓発と早期発見のための方策に関する研究(厚生労働科学研究費補助金に基づく)
2013.06~2017.03, 代表者:井上 博雅, 鹿児島大学, 鹿児島大学大学院医歯学総合研究科
研究課題名を参照。.
研究業績
主要原著論文
1. Takeuchi K, Matsumoto K, Furuta M, Fukuyama S, Takeshita T, Ogata H, Suma S, Shibata Y, Shimazaki Y, Hata J, Ninomiya T, Nakanishi Y, Inoue H, Yamashita Y., Periodontitis is associated with chronic obstructive pulmonary disease.
, J Dent Res
, 98(5): 534-540, 2019.05.
2. Takeuchi K, Matsumoto K, Furuta M, Fukuyama S, Takeshita T, Ogata H, Suma S, Shibata Y, Shimazaki Y, Hata J, Ninomiya T, Nakanishi Y, Inoue H, Yamashita Y., Periodontal status and lung function decline in the community: the Hisayama study., Sci Rep, 8(1): 13354, 2018.01.
3. Kudo K, Hata J, Matsumoto K, Shundo Y, Fukuyama S, Inoue H, Kitazono T, Kiyohara Y, Ninomiya T, Nakanishi Y. , Association of Airflow Limitation with Carotid Atherosclerosis in a Japanese Community‐The Hisayama Study. , Circulation Journal, 81, 1846-1853, 2017.06.
4. Samukawa S, Matsumoto K, Tsukuya G, Koriyama C, Fukuyama S, Uchida A, Mizuno K, Miyahara H, Kiyohara Y, Ninomiya T, Inoue H. , Development a self-scored persistent airflow obstruction screening questionnaire (COPD-Q) in a general Japanese population: the Hisayama study. , Int J COPD
, 12, 1468-1481, 2017.06, BACKGROUND:
The use of a simple screening questionnaire to detect persistent airflow obstruction (AO) in COPD may facilitate the early, accurate diagnosis of COPD in general practice settings.

OBJECTIVE:
This study developed an original persistent AO questionnaire for screening individuals with COPD in a general Japanese population.

METHODS:
A working group was established to generate initial draft questionnaire items about COPD. Eligible subjects aged 40 and older living in Japan were solicited to participate in a health checkup from 2014 to 2015. In study I, 2,338 subjects who fully completed the initial draft questionnaire and who had valid spirometry measurements were statistically analyzed to determine the final questionnaire items as a COPD screening questionnaire (COPD-Q). Persistent AO was defined as a post-bronchodilator FEV1/FVC <0.70. In study II, the working group analyzed the weighted scores for individual items and established a cutoff point for the COPD-Q based on the data of 2,066 subjects in the Hisayama study. Receiver operating characteristic (ROC) curves were used to examine the ability of the COPD-Q to discriminate between subjects with and without AO.

RESULTS:
The five-item COPD-Q was established based on 19 initial draft items in study I and the weighted scores of individual items. The overall area under the ROC curve for the COPD-Q was 0.796 (95% confidence interval, 0.707-0.788). A cutoff of 4 points resulted in a sensitivity of 71.0% and a specificity of 70.1%. The positive predictive value was 10.8%, and the negative predictive value was 97.9%. The crude odds ratio of the COPD-Q for AO was 5.8.

CONCLUSION:
The five-item COPD-Q is a useful questionnaire for diagnosing persistent AO in a general Japanese population and is expected to be an effective first-stage screening tool for detecting COPD..
5. Hamano S, Matsumoto K, Tonai K, Fukuyama S, Kan-o K, Seki N, Inoue H, Nakanishi Y. , Effects of corticosteroid plus long-acting beta2-agonist on the expression of PD-L1 in double-stranded RNA-induced lung inflammation in mice. , J Inflammation.
, 14, 2, 2017.01.
6. Matsumoto K, Seki N, Fukuyama S, Moriwaki A, Kan-o K, Matsunaga Y, Noda N, Yoshida M, Koto H, Takata S, Nakanishi Y, Kiyohara Y, Inoue H, Prevalence of asthma with airflow limitation, COPD, and COPD with variable airflow limitation in older subjects in a general Japanese population. The Hisayama Study., Respiratory Investigation, 53, 22-29, 2015.06.
7. 松元 幸一郎, 福山 聡, Yoichi Nakanishi, Yutaka Kiyohara, 関七重, Prevalence of asthma with airflow limitation, COPD, and COPD with variable airflow limitation in older subjects in a general Japanese population. The Hisayama Study., 53, 22-29, 2015.01.
8. Keiko Kan-o, Koichiro Matsumoto, Yukari Asai-Tajiri, Saaka Hamano, Satoru FUKUYAMA, Nanae Seki, Yoichi Nakanishi, Hiromasa Inoue, PI3K-delta mediates double-stranded RNA-induced upregulation of B7-H1 in BEAS-2B airway epithelial cells., Biochemical and Biophysical Research Communications, 435, 195-201, 2013.05, Airway viral infection disturbs the health-related quality of life. B7-H1 (also known as PD-L1) is a coinhibitory molecule associated with the escape of viruses from the mucosal immunity, leading to persistent infection. Most respiratory viruses generate double-stranded (ds) RNA during replication. The stimulation of cultured airway epithelial cells with an analog of viral dsRNA, polyinosinic-polycytidylic acid (poly IC) upregulates the expression of B7-H1 via activation of the nuclear factor κB(NF-κB). The mechanism of upregulation was investigated in association with phosphatidylinositol 3-kinases (PI3Ks). Poly IC-induced upregulation of B7-H1 was profoundly suppressed by a pan-PI3K inhibitor and partially by an inhibitor or a small interfering (si)RNA for PI3Kδ in BEAS-2B cells. Similar results were observed in the respiratory syncytial virus-infected cells. The expression of p110δ was detected by Western blot and suppressed by pretreatment with PI3Kδ siRNA. The activation of PI3Kδ is typically induced by oxidative stress. The generation of reactive oxygen species was increased by poly IC. Poly IC-induced upregulation of B7-H1 was attenuated by N-acetyl-L-cysteine, an antioxidant, or by oxypurinol, an inhibitor of xanthine oxidase. Poly IC-induced activation of NF-κB was suppressed by a pan-PI3K inhibitor but not by a PI3Kδ inhibitor. These results suggest that PI3Kδ mediates dsRNA-induced upregulation of B7-H1 without affecting the activation of NF-κB..
9. Koichiro Matsumoto, Keiko Kan-o, Satoru FUKUYAMA, Hiromasa Inoue, Yoichi Nakanishi, Mast cells contribute to double-stranded RNA-induced augmentation of airway eosinophilia in a murine model of asthma, 14, 28, 2013.03, Background: Clinical studies showed the contribution of viral infection to the development of asthma. Although mast cells have multiple roles in the pathogenesis of allergic asthma, their role of in the virus-associated pathogenesis of asthma remains unknown. Most respiratory viruses generate double-stranded (ds) RNA during their replication. dsRNA provokes innate immune responses. We recently showed that an administration of polyinocinic polycytidilic acid (poly IC), a mimetic of viral dsRNA, during allergen sensitization augments airway eosinophilia and hyperresponsiveness in mice via enhanced production of IL-13.
Methods: The effect of poly IC on allergen-induced airway eosinophilia was investigated for mast cell-conserved Kit+/+ mice and -deficient KitW/KitW-v mice. The outcome of mast cell reconstitution was further investigated.
Results: Airway eosinophilia and IL-13 production were augmented by poly IC in Kit+/+ mice but not in KitW/KitW-v mice. When KitW/KitW-v mice were reconstituted with bone marrow-derived mast cells (BMMCs), the augmentation was restored. The augmentation was not induced in the mice systemically deficient for TIR domain-containing adaptor-inducing IFN- (TRIF) or interferon regulatory factor (IRF)-3, both mediate dsRNA-triggered innate immune responses. The augmentation was, however, restored in KitW/KitW-v mice reconstituted with TRIF-deficient or IRF-3-deficient BMMCs. Although leukotriene B4 and prostaglandin D2 are major lipid mediators released from activated mast cells, no their contribution was shown to the dsRNA-induced augmentation of airway eosinophilia.
Conclusions: We conclude that mast cells contribute to dsRNA-induced augmentation of allergic airway inflammation without requiring direct activation of mast cells with dsRNA or involvement of leukotriene B4 or prostaglandin D2.
.
10. Koichiro Matsumoto, Yukari Asai, Satoru Fukuyama, Keiko Kan-o, Yuko Matsunaga, Naotaka Noda, Hiroko Kitajima, Kentaro Tanaka, Yoichi Nakanishi, Hiromasa Inoue, IL-6 induced by double-stranded RNA augments allergic inflammation via suppression of Foxp3+T-cell/IL-10 axis, American Journal of Respiratory Cell and Molecular Biology, in press (Epub ahead of print), 2011.07, polycytidilic acid (poly IC), a mimetic of viral dsRNA, during allergen sensitization augments airway eosinophilia and hyperresponsiveness in mice via enhanced production of IL-13 from T cells (Matsumoto et al. AJRCMB 2011, 45: 31-39). However, a phenotype of asthma under severer load of dsRNA remains unknown.
D-galactosamine (D-GalN) is known as a strong sensitizer of poly IC. Mice were treated with poly IC plus D-GalN during allergen sensitization. A sublethal dose of poly IC/D-GalN augmented airway eosinophilia and CD4+T-cell accumulation in the lungs but not airway hyperresponsiveness. The augmented inflammation was associated with decreased IL-10 in the bronchoalveolar lavage fluid and decreased Foxp3+regulatory T cells in the lungs. Serum IL-6 was prominently higher in the mice treated with poly IC/D-GalN than in that with poly IC alone or D-GalN alone. Poly IC/D-GalN failed to augment airway eosinophilia after anti-IL-10 receptor mAb treatment during allergen challenge. Finally, anti-IL-6 receptor mAb treatment before poly IC/D-GalN completely prevented the decrease of IL-10 and Foxp3+regulatory T cells and the augmentation of airway inflammation.
These results indicate that enhanced production of IL-6 by poly IC/D-GalN induces the augmentation of allergic inflammation via suppression of Foxp3+regulatory T cell/IL-10 axis. IL-6 may be a target for preventing asthma augmentation related to severe virus infection.
.
11. Matsumoto K, Kan-O K, Eguchi-Tsuda M, Fukuyama S, Asai Y, Matsumoto T, Moriwaki A, Matsunaga Y, Tsutsui H, Kawai T, Takeuchi O, Akira S, Yagita H, Azuma M, Nakanishi Y, and Inoue H., Essential role of B7-H1 in double-stranded RNA-induced augmentation of an asthma phenotype in mice. , Am J Respir Cell Mol Biol., in press, 2011.06.
12. Koichiro Matsumoto, Hiromasa Inoue, Satoru Fukuyama, Miyuki Eguchi-Tsuda, Takafumi Matsumoto, Atsushi Moriwaki, Takako Nakano, Yoichi Nakanishi, Frequency of Foxp3+CD4+CD25+T cells associates with the phenotypes of allergic asthma, Respirology, 14, 187-194, 2009.05.
13. Matsumoto K, Aizawa H, Inoue R, Hamano S, Ikeda S, Xie Z, Hirata M, Hara N, Ito Y, Effects of epithelial cell supernatant on membrane potential and contraction of dog airway smooth muscles., Am J Respir Cell Mol Biol, 10, 3, 322-330, 10: 322-330, 1994.04.
主要学会発表等
1. 松元 幸一郎,
喘息とCOPDのオーバーラップ症候群「オーバーラップ症候群について:治療を中心に」

(日本アレルギー学会との共同企画)
, 第54回日本呼吸器学会学術講演会 2014年4月25日、大阪, 2014.04.
学会活動
所属学会名
日本結核病学会
日本臨床腫瘍学会
日本内科学会
日本呼吸器学会
日本アレルギー学会
日本免疫学会
日本肺癌学会
学協会役員等への就任
2019.06~2021.06, 日本アレルギー学会, 代議員.
2016.04~2018.03, 日本呼吸器学会, 評議員.
学術論文等の審査
年度 外国語雑誌査読論文数 日本語雑誌査読論文数 国際会議録査読論文数 国内会議録査読論文数 合計
2018年度
2015年度    
2016年度      
2017年度      
その他の研究活動
海外渡航状況, 海外での教育研究歴
McMaster University, Department of Medicine, Division of Respirorogy, Canada, 1998.08~2000.06.
受賞
アボットジャパンアレルギー学術奨励賞, 日本アレルギー協会, 2008.11.
American College of Chest Physicians (ACCP)日本部会賞, American College of Chest Physicians (ACCP)日本部会, 2005.09.
研究資金
科学研究費補助金の採択状況(文部科学省、日本学術振興会)
2019年度~2021年度, 基盤研究(C), 代表, 気道ウィルス感染におけるPD-L2の意義解明とそれに基づく新規治療法の探索.
2012年度~2014年度, 基盤研究(C), 代表, B7-H1発現の薬物的制御によるCOPD・喘息の増悪を目指す基盤研究.
2007年度~2007年度, 基盤研究(C), 代表, 喘息におけるウィルス関連分子2本鎖リボ核酸の病的意義の解明と新規治療法の探索.
2001年度~2001年度, 奨励研究(A), 代表, 気管支喘息におけるインターロイキン10産生T細胞の病態制御的意義についての研究.
2002年度~2002年度, 若手研究(A), 代表, 気管支喘息におけるインターロイキン10産生T細胞の病態制御的意義についての研究.
共同研究、受託研究(競争的資金を除く)の受入状況
2010.10~2011.12, 分担, 気管支喘息に対する新規治療薬KRP108の有用性と安全性を検証する臨床試験(治験).
寄附金の受入状況
2016年度, ノバルティスファーマ, 奨学寄附金.
2016年度, 第一三共, 奨学寄附金.
2017年度, ノバルティスファーマ, 奨学寄附金.
2017年度, アステラス製薬, 奨学寄附金.

九大関連コンテンツ

pure2017年10月2日から、「九州大学研究者情報」を補完するデータベースとして、Elsevier社の「Pure」による研究業績の公開を開始しました。
 
 
九州大学知的財産本部「九州大学Seeds集」