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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

Research Project

Project/Area Number 15K09207
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionTohoku University

Principal Investigator

Tamada Tsutomu  東北大学, 大学病院, 講師 (80396473)

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)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
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)
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
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.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (42 results)

All 2017 2016 2015

All Journal Article (26 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 13 results,  Open Access: 13 results,  Acknowledgement Compliant: 3 results) Presentation (16 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [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.
    • Journal Title

      Pharmacoepidemiol Drug Saf.

      Volume: 26 Issue: 10 Pages: 1182-1189

    • DOI

      10.1002/pds.4259

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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
    • Journal Title

      Thorax

      Volume: 72 Issue: 12 Pages: 1074-1083

    • DOI

      10.1136/thoraxjnl-2016-209359

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      Thorax

      Volume: 2017 Issue: 10 Pages: 893-904

    • DOI

      10.1136/thoraxjnl-2016-209352

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 特集COPDと喘息の最新治療 「COPDと喘息の病態生理」2017

    • Author(s)
      玉田 勉、一ノ瀬正和
    • Journal Title

      臨牀と研究

      Volume: 94 Pages: 5-10

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 特集 「喘息と COPDのオーバラップ症候群― 病態と治療」 ACOSの疾患概念2017

    • Author(s)
      玉田 勉、 一ノ瀬正和
    • Journal Title

      アレルギーの臨床

      Volume: 37 Pages: 17-21

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Leukotriene Receptor Antagonists and Antiallergy Drugs.2017

    • Author(s)
      Tamada T, Ichinose M.
    • Journal Title

      Handb Exp Pharmacol.

      Volume: 237 Pages: 153-169

    • DOI

      10.1007/164_2016_72

    • ISBN
      9783319521732, 9783319521756
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Coexisting COPD in elderly asthma with fixed airflow limitation: assessment by DLco %predicted and HRCT.2017

    • Author(s)
      Tamada T, Sugiura H, Takahashi T, Matsunaga K, Kimura K, Katsumata U, Ohta K, Ichinose M.
    • Journal Title

      J Asthma

      Volume: 印刷中 Issue: 6 Pages: 1-9

    • DOI

      10.1080/02770903.2016.1247168

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Lymphocyte Kv1.3-Channels in the Pathogenesis of Chronic Obstructive Pulmonary Disease: Novel Therapeutic Implications of Targeting the Channels by Commonly Used Drugs2016

    • Author(s)
      Kazama I, Tamada T.
    • Journal Title

      Allergy Asthma Clin Immunol.

      Volume: 29 Issue: 1 Pages: 60-60

    • DOI

      10.1186/s13223-016-0168-3

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] itreous lavage fluid and bronchoalveolar lavage fluid have equal diagnostic value in sarcoidosis.2016

    • Author(s)
      Maruyama K, Inaba T, Tamada T, Kunikata H, Nakazawa T.
    • Journal Title

      Medicine (Baltimore)

      Volume: 95 Issue: 49 Pages: e5531-e5531

    • DOI

      10.1097/md.0000000000005531

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [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
    • Journal Title

      AnnalsATS

      Volume: 13 Issue: 11 Pages: 1912-1922

    • DOI

      10.1513/annalsats.201605-335oc

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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.
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol

      Volume: 310 Issue: 11 Pages: L1028-L1041

    • DOI

      10.1152/ajplung.00351.2015

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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.
    • Journal Title

      BMC Pulm Med.

      Volume: 16 Issue: 1 Pages: 30-30

    • DOI

      10.1186/s12890-016-0193-5

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Case of Acute Sarcoidosis with Fever and Polyarthralgia2016

    • Author(s)
      小野寺克洋、玉田 勉、村松聡士、村上康司、奈良正之、小松理世、小林 誠、山田充啓、杉浦久敏、一ノ瀬正和
    • Journal Title

      Nihon Naika Gakkai Zasshi

      Volume: 105 Issue: 3 Pages: 540-546

    • DOI

      10.2169/naika.105.540

    • NAID

      130005439474

    • ISSN
      0021-5384, 1883-2083
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 喘息における長時間作用性吸入抗コリン薬2016

    • Author(s)
      玉田 勉
    • Journal Title

      アレルギーの臨床

      Volume: 36 Pages: 22-26

    • Related Report
      2016 Research-status Report 2015 Research-status Report
  • [Journal Article] 閉塞性肺疾患(SASを含む)2016

    • Author(s)
      玉田 勉
    • Journal Title

      EBM 呼吸器疾患の治療

      Volume: 1 Pages: 31-36

    • Related Report
      2016 Research-status Report
  • [Journal Article] ACOSを巡る新しい話題2016

    • Author(s)
      玉田 勉、一ノ瀬正和
    • Journal Title

      Annual Review 2016 呼吸器

      Volume: 1 Pages: 137-144

    • Related Report
      2016 Research-status Report 2015 Research-status Report
  • [Journal Article] Toll様受容体システムの気道分泌への関与2016

    • Author(s)
      玉田 勉
    • Journal Title

      アレルギーの臨床

      Volume: 26 Pages: 45-51

    • Related Report
      2016 Research-status Report 2015 Research-status Report
  • [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.
    • Journal Title

      Respir Res

      Volume: 17 Issue: 1 Pages: 7-7

    • DOI

      10.1186/s12931-016-0322-y

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biomarker-based detection of ACOS in COPD populations.2015

    • Author(s)
      Tamada, T., H. Sugiura, T. Takahashi, K. Matsunaga, K. Kimura, U. Katsumata, D. Takekoshi, T. Kikuchi, K. Ohta and M. Ichinose.
    • Journal Title

      Int J Chron Obstruct Pulmon Di

      Volume: 10 Pages: 2169-2176

    • DOI

      10.2147/copd.s88274

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 喘息予防・管理ガイドライン2015改訂のポイントと今後の展望 3-1) 気道炎症の評価2015

    • Author(s)
      玉田 勉
    • Journal Title

      Progress in Medicine

      Volume: 35 Pages: 1541-1547

    • Related Report
      2015 Research-status Report
  • [Journal Article] 呼吸器疾患の新治療「スピオルト・レスピマット」2015

    • Author(s)
      玉田 勉、一ノ瀬正和
    • Journal Title

      呼吸

      Volume: 35 Pages: 994-1003

    • Related Report
      2015 Research-status Report
  • [Journal Article] アレルギー疾患のフェノタイプとエンドタイプ 『COPDを合併する喘息の病態と治療』2015

    • Author(s)
      玉田 勉、一ノ瀬正和
    • Journal Title

      アレルギー・免疫

      Volume: 22 Pages: 60-71

    • Related Report
      2015 Research-status Report
  • [Journal Article] 呼吸器疾患の新治療「アノーロ」2015

    • Author(s)
      玉田 勉、一ノ瀬正和
    • Journal Title

      呼吸

      Volume: 34 Pages: 491-500

    • Related Report
      2015 Research-status Report
  • [Journal Article] 解説 COPDとのオーバーラップ:Asthma COPD overlap syndrome(ACOS)2015

    • Author(s)
      玉田 勉、一ノ瀬正和
    • Journal Title

      呼吸器内科

      Volume: 27 Pages: 228-235

    • Related Report
      2015 Research-status Report
  • [Journal Article] 気管・気管支軟化症2015

    • Author(s)
      奈良正之、玉田 勉
    • Journal Title

      呼吸

      Volume: 33 Pages: 304-308

    • Related Report
      2015 Research-status Report
  • [Journal Article] 気管支喘息の気道炎症を反映するバイオマーカー2015

    • Author(s)
      玉田 勉、一ノ瀬正和
    • Journal Title

      内科 アレルギー・免疫

      Volume: 22 Pages: 28-37

    • Related Report
      2015 Research-status Report
  • [Presentation] Upregulation of Ca2+-ATPase by TLR7 Decreases Electrolyte Secretion from Airway Submucosal Gland Cells2017

    • Author(s)
      Gamo S, Tamada T, Murakami K, Muramatsu S, Aritake H, Nara M, Kazama I, Sugiura H, Ichinose M.
    • Organizer
      2017 ATS International Conference in Washington DC
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 客観的指標を用いたCOPD合併喘息の検討2017

    • Author(s)
      玉田 勉、杉浦 久敏、高橋 識至、松永 和人、勝又 宇一郎、木村 啓二、大田 健、一ノ瀬 正和
    • Organizer
      第51回 東北アレルギー懇話会
    • Related Report
      2017 Annual Research Report
  • [Presentation] TLR7リガンドによる気道分泌抑制作用の細胞内機序について2017

    • Author(s)
      蒲生俊一、玉田 勉、村上康司、村松聡士、有竹秀美 、奈良正之、風間逸郎 、杉浦久敏、一ノ瀬正和
    • Organizer
      第57回日本呼吸器学会学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 客観的指標を用いたCOPD合併喘息の検討2017

    • Author(s)
      玉田 勉、杉浦 久敏、高橋 識至、松永 和人、勝又 宇一郎、木村 啓二、大田 健、一ノ瀬 正和
    • Organizer
      第57回日本呼吸器学会学術講演会
    • Related Report
      2017 Annual Research Report
  • [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
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Toll like receptor 7 regulates the electrolytes secretion from airway submucosal gland.2016

    • Author(s)
      Gamo S, Muramatsu S, Murakami K, Tamada T, Nara M, Sugiura H, Ichinose M.
    • Organizer
      2016 ATS International Conference
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 当院科外来で全身性サルコイドーシスのフォロー中、寛解後に増悪を認めた症例の臨床的検討2016

    • Author(s)
      蒲生俊一、玉田 勉、村松聡士、村上康司、奈良正之、杉浦久敏、一ノ瀬正和
    • Organizer
      第36回日本サルコイドーシス/肉芽腫性疾患学会総会
    • Place of Presentation
      東京、東京医科歯科大学 M&Dタワー2階 鈴木章夫記念講堂
    • Related Report
      2016 Research-status Report
  • [Presentation] 組織学的に診断された卵管サルコイドーシスの1例2016

    • Author(s)
      村松聡士、玉田 勉、奈良正之、村上康司、蒲生俊一、丸山和一、久野貴司、立花眞仁、杉浦久敏、八重樫伸生、一ノ瀬正和
    • Organizer
      第36回日本サルコイドーシス/肉芽腫性疾患学会総会
    • Place of Presentation
      東京、東京医科歯科大学 M&Dタワー2階 鈴木章夫記念講堂
    • Related Report
      2016 Research-status Report
  • [Presentation] バイオマーカーに基づく喘息-COPDオーバーラップ症候群の検出2016

    • Author(s)
      玉田 勉、杉浦久敏、高橋識至、松永和人、勝又宇一郎、木村啓二、大田 健、一ノ瀬正和
    • Organizer
      第56回日本呼吸器学会学術講演会
    • Place of Presentation
      京都、国立京都国際会館
    • Related Report
      2016 Research-status Report
  • [Presentation] TLR7の気道粘膜下腺細胞での発現と分泌機能への影響2016

    • Author(s)
      蒲生俊一、玉田 勉、村松聡士、奈良正之、村上康司、杉浦久敏、一ノ瀬正和
    • Organizer
      第56回日本呼吸器学会学術講演会
    • Place of Presentation
      京都、国立京都国際会館
    • Related Report
      2016 Research-status Report
  • [Presentation] メタボロミクス解析を用いたサルコイドーシス新規バイオマーカーの検索2016

    • Author(s)
      村松聡士, 玉田 勉, 三枝大輔, 奈良正之, 蒲生俊一, 村上康司, 杉浦久敏, 一ノ瀬正和
    • Organizer
      第56回日本呼吸器学会学術講演会
    • Place of Presentation
      京都、国立京都国際会館
    • Related Report
      2016 Research-status Report
  • [Presentation] 最近のCOPD治療薬に期待する効果とそのエビデンス2015

    • Author(s)
      玉田 勉
    • Organizer
      第85回日本呼吸器学会近畿地方会 ランチョンセミナー①
    • Place of Presentation
      奈良県文化会館(奈良市)
    • Year and Date
      2015-07-11
    • Related Report
      2015 Research-status Report
  • [Presentation] Effects of TLR ligands on the intracellular calcium signaling in tracheal submucosal gland acinar cells.2015

    • Author(s)
      Muramatsu, S., T. Tamada, M. Nara, S. Gamow, K. Murakami, T. Kikuchi and M. Ichinose.
    • Organizer
      ATS 2015 International Conference
    • Place of Presentation
      Denver, CO, USA
    • Year and Date
      2015-05-16
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 気道分泌調整因子としてのTLRリガンドの細胞内カルシウム濃度への影響2015

    • Author(s)
      蒲生俊一、玉田 勉、村松聡士、村上康司、奈良正之、菊地利明、一ノ瀬正和
    • Organizer
      第55回日本呼吸器学会学術講演会
    • Place of Presentation
      東京国際フォーラム(東京都)
    • Year and Date
      2015-04-19
    • Related Report
      2015 Research-status Report
  • [Presentation] 診断基準改訂前後の当科におけるサルコイドーシスと悪性腫瘍の合併例の検討2015

    • Author(s)
      村松聡士、玉田 勉、奈良正之、村上康司、蒲生俊一、菊地利明、一ノ瀬正和
    • Organizer
      第55回日本呼吸器学会学術講演会
    • Place of Presentation
      東京国際フォーラム(東京都)
    • Year and Date
      2015-04-18
    • Related Report
      2015 Research-status Report
  • [Presentation] 東北大学病院呼吸器バイオバンクの現状と課題2015

    • Author(s)
      宮内栄作、光石陽一郎、東出直樹、椎原淳、三橋善哉、村松聡士、小林誠、佐藤輝幸、玉井ときわ、山田充啓、小荒井晃、井上彰、岡崎達馬、大河内眞也、玉田 勉、杉浦久敏、一ノ瀬正和
    • Organizer
      第55回日本呼吸器学会学術講演会
    • Place of Presentation
      東京国際フォーラム(東京都)
    • Year and Date
      2015-04-17
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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