2017 Fiscal Year Final Research Report
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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| Keywords | 気道分泌 / 微生物叢 / Toll様受容体 / COPD増悪 / 重症喘息 |
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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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| Free Research Field |
呼吸器内科学
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