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