Detection of specific antigens from lung microbiome causing a dysfunction of airway mucociliary transport and its regulation of those signaling in chronic inflammatory airway diseases
| Project/Area Number |
15K09207
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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 | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
村松 聡士 東北大学, 医学系研究科, 大学院非常勤講師 (30732549)
奈良 正之 東北大学, 大学病院, 特任教授 (70374999)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 気道分泌 / 微生物叢 / Toll様受容体 / COPD増悪 / 重症喘息 / 過分泌 / 気道粘膜下腺 / パッチクランプ / 難治性喘息 |
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| Outline of Final Research Achievements |
Little is known about the impact of innate immunity including Toll-like receptors (TLRs) on airway secretion. Here, we investigated whether TLR7 has a significant effect on physiological airway secretion from tracheal submucosal glands(SMG). Patch-clamp analyses revealed that TLR7 ligand inhibited the ACh-induced ionic currents. Intracellular calcium assays revealed that TLR7 attenuated the transient rises in the intracellular Ca2+ concentration ([Ca2+]i). Immunofluorescent staining revealed that TLR7 was co-localized with SERCA2. TLR7 expression was downregulated in COPD airways. These findings suggest that an activation of TLR7 accelerates the SERCA2-induced Ca2+ clearance, and that both a dysfunction of TLR7 and hyperactivation of TLR4/5 act together to cause prolonged airway hypersecretion. Improvement of TLR7 dysfunction could be a novel treatment for reducing the risk of exacerbations of COPD by controlling airway secretion.
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Report
(4 results)
Research Products
(42 results)
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[Journal Article] Risk factors for stomatitis in patients with lymphangioleiomyomatosis during treatment with sirolimus: A multicenter investigator-initiated prospective study.2017
Author(s)
Kitamura N, Seyama K, Inoue Y, Nagai K, Suzuki M, Moriyama H, Takada T, Tazawa R, Hirai T, Mishima M, Hayashida M, Hirose M, Arai T, Sugimoto C, Hattori N, Watanabe K, Tamada T, Akazawa K, Tanaka T, Nakata K.
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Journal Title
Pharmacoepidemiol Drug Saf.
Volume: 26
Issue: 10
Pages: 1182-1189
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Production of reactive persulfide species in chronic obstructive pulmonary disease2017
Author(s)
Numakura T, Sugiura H, Akaike T, Ida T, Fujii S, Koarai A, Yamada M, Onodera K, Hashimoto Y, Tanaka R, Sato K, Shishikura Y, Hirano T, Yanagisawa S, Fujino N, Okazaki T, Tamada T, Hoshikawa Y, Okada Y, Ichinose M
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Journal Title
Thorax
Volume: 72
Issue: 12
Pages: 1074-1083
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Decrease in an anti-ageing factor, growth differentiation factor 11, in chronic obstructive pulmonary disease.2017
Author(s)
Onodera K, Sugiura H, Yamada M, Koarai A, Fujino N, Yanagisawa S, Tanaka R, Numakura T, Togo S, Sato K, Kyogoku Y, Hashimoto Y, Okazaki T, Tamada T, Kobayashi S, Yanai M, Miura M, Hoshikawa Y, Okada Y, Suzuki S, Ichinose M.
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Journal Title
Thorax
Volume: 2017
Issue: 10
Pages: 893-904
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Efficacy and Safety of Long-Term Sirolimus Therapy for Asian Patients with Lymphangioleiomyomatosis2016
Author(s)
Takada T, Mikami A, Kitamura N, Seyama K, Inoue Y, Nagai K, Suzuki M, Moriyama H, Akasaka K, Tazawa R, Hirai T, Mishima M, Hayashida M, Hirose M, Sugimoto C, Arai T, Hattori N, Watanabe K, Tamada T, Yoshizawa H, Akazawa K, Tanaka T, Yagi K, Young LR, McCormack FX, Nakata K
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Journal Title
AnnalsATS
Volume: 13
Issue: 11
Pages: 1912-1922
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] 27-hydroxycholesterol accelerates cellular senescence in human lung resident cells.2016
Author(s)
Hashimoto Y, Sugiura H, Togo S, Koarai A, Abe K, Yamada M, Ichikawa T, Kikuchi T, Numakura T, Onodera K, Tanaka R, Sato K, Yanagisawa S, Okazaki T, Tamada T, Kikuchi T, Hoshikawa Y, Okada Y, Ichinose M.
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Journal Title
Am J Physiol Lung Cell Mol Physiol
Volume: 310
Issue: 11
Pages: L1028-L1041
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Simultaneous development of sarcoidosis and cutaneous vasculitis in a patient with refractory Crohn's disease during infliximab therapy.2016
Author(s)
Numakura T, Tamada T, Nara M, Muramatsu S, Murakami K, Kikuchi T, Kobayashi M, Muroi M, Okazaki T, Takagi S, Eishi Y, Ichinose M.
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Journal Title
BMC Pulm Med.
Volume: 16
Issue: 1
Pages: 30-30
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Possible role of Krüppel-like factor 5 in the remodeling of small airways and pulmonary vessels in chronic obstructive pulmonary disease.2016
Author(s)
Abe. K., H. Sugiura, Y. Hashimoto, T. Ichikawa, A. Koarai, M. Yamada, T. Numakura, K. Onodera, R. Tanaka, K. Sato, S. Yanagisawa, T. Okazaki, T. Tamada, T. Kikuchi and M. Ichinose.
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Journal Title
Respir Res
Volume: 17
Issue: 1
Pages: 7-7
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Comorbidity in asthma2017
Author(s)
Tsutomu Tamada
Organizer
The 6th Conference of International Union Against Tuberculosis and Lung Disease Asia Pacific Region, 2017
Place of Presentation
Tokyo, Tokyo International Forum
Related Report
Int'l Joint Research / Invited
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