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Investigation of molecular basis of exacerbation in chronic respiratory disease caused by respiratory infection

Research Project

Project/Area Number 16H05310
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNara Medical University

Principal Investigator

Ito Toshihiro  奈良県立医科大学, 医学部, 教授 (00595712)

Co-Investigator(Kenkyū-buntansha) 笠原 敬  奈良県立医科大学, 医学部, 病院教授 (50405403)
北畠 正大  奈良県立医科大学, 医学部, 講師 (60457588)
松川 昭博  岡山大学, 医歯薬学総合研究科, 教授 (90264283)
友田 恒一  川崎医科大学, 医学部, 教授 (90364059)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2016: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywordsエピジェネティクス / 慢性呼吸器疾患 / 呼吸器感染症 / 慢性炎症 / インフルエンザウイルス / 肺炎球菌 / 免疫学 / エピジェネチティクス / エピゲネティクス / ウィルス / 細菌 / 内科 / エピジェネ手ィクス / 感染症 / 遺伝学
Outline of Final Research Achievements

Patients who have a chronic respiratory disease have a very high risk of respiratory infection due to viruses and bacteria, and it is necessary to elucidate the pathological condition and molecular mechanism and identify the factors that affect each other's diseases. In this study, we focused on SET domain, bifurcated 2 (SETDB2), which is one of the histone H3K9 (9th lysine) methylase, and the expression of SETDB2 showed a significant increase in the chronic respiratory disease model. The importance of SETDB2 in respiratory diseases was clarified by increasing the expression in chronic respiratory diseases and respiratory infections and by indicating the role of SETDB2 in pathological conditions.

Academic Significance and Societal Importance of the Research Achievements

肺気腫や肺線維症といった慢性呼吸器疾患は有効な治療法がなく、これらを基礎疾患として有する患者はウィルスや細菌による呼吸器感染症のリスクが非常に高く、呼吸器感染症に伴う基礎疾患の急性増悪は患者のQOL (Quality of life)を著しく低下させ、予後にも多大な影響を及ぼす。感染による基礎疾患の急性増悪の予防や治療成績の改善には、慢性呼吸器疾患と呼吸器感染症それぞれの病態・分子機構の解明、そして相互の疾患に影響を与える因子の同定が必要であり、本研究においてSETDB2が慢性呼吸器疾患と呼吸器感染症それぞれの病態に深く関わることを見出した学術的意義・社会的意義はは大きいと考える。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (30 results)

All 2020 2019 2018 2017 2016 Other

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 7 results) Presentation (18 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Respiratory Syncytial Virus Infection Exacerbates Pneumococcal Pneumonia via Gas6/Axl-mediated Macrophage Polarization2020

    • Author(s)
      Shibata T, Makino A, Ogata R, Nakamura S, Ito T, Nagata K, Terauchi Y, Oishi T, Fujieda M, Takahashi Y, Ato M.
    • Journal Title

      J Clin Invest .

      Volume: 6 Issue: 6 Pages: 3021-3037

    • DOI

      10.1172/jci125505

    • NAID

      120007017546

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Abrogated Caveolin-1 expression via histone modification enzyme Setdb2 regulates brain edema in a mouse model of influenza-associated encephalopathy.2019

    • Author(s)
      Imakita N, Kitabatake M, Ouji-Sageshima N, Hara A, Morita-Takemura S, Kasahara K, Matsukawa A, Wanaka A, Mikasa K, Ito T.
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 284-284

    • DOI

      10.1038/s41598-018-36489-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Young adult patients with squamous cell carcinoma of the tongue strongly express p16 without human papillomavirus infection2019

    • Author(s)
      Tachibana Tomoyasu、Orita Yorihisa、Gion Yuka、Miki Kentaro、Ikegami Kana、Marunaka Hidenori、Makino Takuma、Akagi Yusuke、Akisada Naoki、Tsumura Munechika、Ito Toshihiro、Yoshino Tadashi、Nishizaki Kazunori、Sato Yasuharu
    • Journal Title

      Acta Oto-Laryngologica

      Volume: 139 Issue: 1 Pages: 80-84

    • DOI

      10.1080/00016489.2018.1541506

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Responses of perivascular macrophages to circulating lipopolysaccharides in the subfornical organ with special reference to endotoxin tolerance.2019

    • Author(s)
      Morita-Takemura S, Nakahara K, Hasegawa-Ishii S, Isonishi A, Tatsumi K, Okuda H, Tanaka T, Kitabatake M, Ito T, Wanaka A.
    • Journal Title

      J Neuroinflammation

      Volume: 16 Issue: 1 Pages: 39-51

    • DOI

      10.1186/s12974-019-1431-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Osteogenesis of osteogenic matrix cell sheets preserved in culture medium in a rat model2018

    • Author(s)
      Kira Tsutomu、Akahane Manabu、Ouji-Sageshima Noriko、Shimizu Takamasa、Onishi Tadanobu、Omokawa Shohei、Ito Toshihiro、Tanaka Yasuhito
    • Journal Title

      Cell Transplantation

      Volume: 27 Issue: 8 Pages: 1281-1288

    • DOI

      10.1177/0963689718786233

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spred2-deficiecy Protects Mice from Polymicrobial Septic Peritonitis by Enhancing Inflammation and Bacterial Clearance2017

    • Author(s)
      Itakura Junya、Sato Miwa、Ito Toshihiro、Mino Megumi、Fushimi Soichiro、Takahashi Sakuma、Yoshimura Teizo、Matsukawa Akihiro
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 12833-12833

    • DOI

      10.1038/s41598-017-13204-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Persimmon-derived tannin has bacteriostatic and anti-inflammatory activity in a murine model of Mycobacterium avium complex (MAC) disease2017

    • Author(s)
      Yoko Matsumura, Masahiro Kitabatake, Noriko Ouji-Sageshima, Satsuki Yasui, Naoko Mochida, Ryuichi Nakano, Kei Kasahara, Koichi Tomoda, Hisakazu Yano, Shin-ichi Kayano, Toshihiro Ito
    • Journal Title

      PLoS One

      Volume: 12 Issue: 8 Pages: e0183489-e0183489

    • DOI

      10.1371/journal.pone.0183489

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Silencing of Carbohydrate Sulfotransferase 15 Hinders Murine Pulmonary Fibrosis Development2017

    • Author(s)
      Yoshiro Kai, Koichi Tomoda, Hiroyuki Yoneyama, Masahiro Kitabatake, Atsuhiro Nakamura, Toshihiro Ito, Masanori Yoshikawa, and Hiroshi Kimura.
    • Journal Title

      Molecular Therapy - Nucleic Acids

      Volume: 6 Pages: 163-172

    • DOI

      10.1016/j.omtn.2016.12.008

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sprouty-Related Ena Vasodilator-Stimulated Phosphoprotein Homology 1-Domain Containing Protein-2 Critically Regulates Influenza A Virus Induced Pneumonia2016

    • Author(s)
      Toshihiro Ito, Junya Itakura, Sakuma Takahashi, Miwa Sato, Megumi Mino, Soichiro Fushimi, Masao Yamada, Tuneo Morishima, Steven L. Kunkel, Akihiro Matsukawa
    • Journal Title

      Critical Care Medicine

      Volume: 44 Issue: 7 Pages: e530-e543

    • DOI

      10.1097/ccm.0000000000001562

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Immune and epigenetic regulation through histone-lysine N-methyltransferase Setdb2 during severe influenza virus infection2020

    • Author(s)
      Toshihiro Ito, Natsuko Imakita, Atsushi Hara, Noriko Ouji-Sageshima, Masahiro Kitabatake
    • Organizer
      IMMUNOLOGY 2020
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] エピジェネティクスによる重症インフルエンザウイルス感染症の病態解明から創薬展開へ2020

    • Author(s)
      伊藤 利洋、今北 菜津子、王寺 典子、北畠 正大
    • Organizer
      日本薬学会140年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] The contribution of hirtone-lysine N-methyltransferase Setdb2 in high mortality of secondary bacterial pneumonia via regulating cytokines and chemokines in macrophages.2019

    • Author(s)
      Hara Atushi, Kitabatake Masahiro. Ouji-Sageshima Noriko, Sonobe Shota, Imakita Natsuko, Furukawa Ryutaro, Oda Akihisa, Ito Toshihiro
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] HLA-F could be a specific target for both pathological diagnosis and cancer immunotherapy of malignant colon cancer2019

    • Author(s)
      Ouji-Sageshima Noriko, Nishioka Tatsuki, Kitabatake Masahiro, Geraghty E. Daniel , Ishitani Akiko, Ito Toshihiro
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Cigarette smoke has different effects on inflammatory bowel disease model through mucosal immunity and gut microbiota2019

    • Author(s)
      Nishioka Tatsuki, Kitabatake Masahiro. Ouji-Sageshima Noriko, Nishimura Tomoko, Ito Toshihiro
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Persimmon-derived tannin attenuates the murine model of ulcerative colitis through the alternation of gut environment2019

    • Author(s)
      Kitabatake Masahiro, Matsumura Yoko, Ouji-Sageshima Noriko, Ito Toshihiro.
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Histone modification enzyme SET domain bifurcated 2 (Setdb2) regulates acute inflammation in murine models of acute respiratory distress syndrome (ARDS)2019

    • Author(s)
      Sonobe Shota, Kitabatake Masahiro, Imakita Natsuko, Hara Atsushi, Furukawa Ryutaro, Nishimura Tomoko, Ouji-Sageshima Noriko, Ito Toshihiro
    • Organizer
      第48回日本免疫学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] HLA-F分子を標的とした免疫療法の開発に向けて2019

    • Author(s)
      王寺-下嶋典子、石谷昭子、Daniel E Geraghty、伊藤利洋
    • Organizer
      第28回日本組織適合性学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Adipose-derived mesenchymal stem cell (ADSC) attenuates pulmonary fibrosis in both bleomycin-induced and humanized mice model2018

    • Author(s)
      Toshihiro Ito, Masahiro Kitabatake, Makiko Kumamoto, Aiko Hiyama, Natsuko Imakita, Noriyoshi Sawabata, Noriko Ouji-Sageshima
    • Organizer
      International Society for Stem Cell Research Annual Meeting 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Adipose derived mesenchymal stem cells (ASCs) have anti-fibrotic effects in lung fibroblasts from Idiopathic pulmonary fibrosis (IPF) patients2018

    • Author(s)
      Aiko Hiyama, Noriko Ouji-Sageshima, Masahiro Kitabatake, Makiko Kumamoto, Noriyoshi Sawabata, Toshihiro Ito
    • Organizer
      International Society for Stem Cell Research Annual Meeting 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Histone modification enzyme Setdb2 plays a critical role in a murine model of influenza associated encephalopathy.2018

    • Author(s)
      Natsuko Imakita, Masahiro Kitabatake, Noriko Ouji-Sageshima, Toshihiro Ito
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Enhanced expression of HLA-F is critically related with tumor malignancy2018

    • Author(s)
      Noriko- Ouji-Sageshima, Akiko Ishitani, Daniel E. Geraghty, Nastuk Imakita, Shota Sonobe, Masahiro Kitabatake, Toshihiro Ito
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] The critical role of Epigenetic regulation by Setdb2 in acute respiratory distress syndrome (ARDS) model2018

    • Author(s)
      Shota Sonobe, Masahiro Kitabatake, Noriko Ouji-Sageshima, Natsuko Imakita, Toshihiro Ito
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Cigarette smoke suppresses the ulcerative colitis model through the alteration of immune response and microbiota.2018

    • Author(s)
      Masahiro Kitabatake, Noriko Ouji-Sageshima, Natsuko Imakita, Toshihiro Ito
    • Organizer
      第47回日本免疫学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 重症インフルエンザウイルス感染症の免疫機構2018

    • Author(s)
      伊藤 利洋
    • Organizer
      第410回川崎医学会講演会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] The contribution of histone methyltransferase Setdb2 in the pathogenesis of influenza associated encephalopathy2017

    • Author(s)
      Natsuko Imakita, Masahiro Kitabatake, Noriko Ouji-Sageshima, Shota Sonobe, Toshihiro Ito
    • Organizer
      The 46th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2017 Annual Research Report
  • [Presentation] CD8+ T cells play a critical role for the murine model of immune reconstitution inflammatory syndrome2017

    • Author(s)
      Masahiro Kitabatake, Mitsuru Konishi, Yoko Matsumura, Noriko Ouji-Sageshima, Natsuko Imakita, Toshihiro Ito
    • Organizer
      The 46th Annual Meeting of The Japanese Society for Immunology
    • Related Report
      2017 Annual Research Report
  • [Presentation] The critical role of histone methyltransferase Setdb2 in the pathogenesis of influenza associated encephalopathy2016

    • Author(s)
      Natsuko Imakita, Masahiro Kitabatake, Noriko Ouji-Sageshima, Toshihiro Ito
    • Organizer
      第45回日本免疫学会総会・学術集会
    • Place of Presentation
      沖縄コンベンションセンター
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Book] BIO Clinica2019

    • Author(s)
      伊藤 利洋
    • Total Pages
      5
    • Publisher
      北隆館
    • Related Report
      2019 Annual Research Report
  • [Remarks] 奈良県立医科大学免疫学講座ホームページ

    • URL

      http://www.naramed-u.ac.jp/~immuno/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 奈良県立医科大学免疫学講座

    • URL

      http://www.naramed-u.ac.jp/~immuno/

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2021-02-19  

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