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The analysis of mechanism in the serious inflammatory responses induced by dead cells as aging.

Research Project

Project/Area Number 15K07949
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biological pharmacy
Research InstitutionToho University

Principal Investigator

NAGATA Kisaburo  東邦大学, 理学部, 教授 (10291155)

Co-Investigator(Kenkyū-buntansha) 小林 芳郎  東邦大学, 理学部, 教授 (10134610)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords老化 / アポトーシス / 炎症 / マクロファージ / 死細胞 / 貪食 / アポトーシス細胞
Outline of Final Research Achievements

We investigated why inflammatory responses was increased in aged mice upon injection of dead cells and why the phagocytic capacity of peritoneal resident macrophages from aged mice was reduced. When cocultured with dead cells, the peritoneal resident macrophages from aged mice significantly produced MIP-2, whereas MIP-2 production by macrophages from WT young mice required IFN-γ. The peritoneal resident macrophages from aged mice expressed CD40, a M1 macrophage marker, as in the case of M1 macrophages. Furthermore, M1 macrophages exhibited less phagocytic capacity as to dead cells than non-treated macrophages. These results suggest that the phenotype of peritoneal resident macrophages is skewed toward M1-like in aged mice and that such skewing toward M1-like is involved in enhancement of inflammatory responses induced by dead cells in aged mice.

Report

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

    (14 results)

All 2017 2016 2015

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Acknowledgement Compliant: 1 results) Presentation (11 results)

  • [Journal Article] Skewing of peritoneal resident macrophages toward M1-like is involved in enhancement of inflammatory responses induced by secondary necrotic neutrophils in aged mice.2016

    • Author(s)
      Takahashi R, Ishigami A, Kobayashi Y, Nagata K.
    • Journal Title

      Cell Immunol.

      Volume: 304-305 Pages: 44-48

    • DOI

      10.1016/j.cellimm.2016.03.001

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Suppression of macrophage-mediated phagocytosis of apoptotic cells by soluble β-glucan due to a failure of PKC-βII translaction.2016

    • Author(s)
      Sekiguchi, S., Tomisawa, Y., Ohki, T., Tsuboi, K., Nagata, K., and Kobayashi, Y.
    • Journal Title

      Int. Immunopharm.

      Volume: 31 Pages: 195-199

    • DOI

      10.1016/j.intimp.2015.12.028

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Attenuated phagocytosis of secondary necrotic neutrophils by macrophages in aged and SMP30 knockout mice2015

    • Author(s)
      1.Takahashi, R., Totsuka, S., Ishigami, A., Kobayashi Y., and Nagata, K.
    • Journal Title

      Geriatr. Gerontol. Internal.

      Volume: 17 Issue: 1 Pages: 1111-1111

    • DOI

      10.1111/ggi.12436

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] ネクローシス細胞により誘発される炎症応答の終息と好酸球の関わり2017

    • Author(s)
      懸川奈央、佐藤麻実、石神昭人、小林芳郎、永田喜三郎
    • Organizer
      生命科学系学会合同年次大会 (第40回日本分子生物学会集会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 腹腔常在性マクロファージの貪食応答に対する環境エンリッチメントの効果2017

    • Author(s)
      大滝桃子、小鹿成二、西村まゆみ、柿沼志津子、島田義也、小林芳郎、永田喜三郎
    • Organizer
      生命科学系学会合同年次大会 (第40回日本分子生物学会集会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] がン抑制遺伝子PHLDA3の機能喪失性変異と機能解析2017

    • Author(s)
      冨永航平、西川雷羅、山口陽子、永田喜三郎、大木理恵子
    • Organizer
      生命科学系学会合同年次大会 (第40回日本分子生物学会集会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒト培養表皮を用いたアスコルビン酸の紫外線による細胞傷害抑制効果および関連遺伝子発現への影響2017

    • Author(s)
      河島早紀、滝野有花、近藤嘉高、永田喜三郎、斉藤紀克、大澤肇、栗田克己、佐藤安訓、吉田雅幸、石神昭人
    • Organizer
      生命科学系学会合同年次大会 (第40回日本分子生物学会集会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] マクロファージRAW264.7細胞から放出されるエクソソームの定量プロテオーム解析2017

    • Author(s)
      宮崎優輝、藤田泰典、川上恭司郎、永田喜三郎、伊藤雅史
    • Organizer
      生命科学系学会合同年次大会 (第40回日本分子生物学会集会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Akt抑制因子PHLDA3の新規結合分子PH3IPはAkt活性を制御する2017

    • Author(s)
      山口陽子、西川雷羅、陳ヨ、斉藤梢、広川貴次、八田知久、夏目徹、永田喜三郎、大木理恵子
    • Organizer
      生命科学系学会合同年次大会 (第40回日本分子生物学会集会)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Identification and functional analysis of loss-of-functional mutations of the tumor suppressor gene PHLDA3 in various cancer types.2016

    • Author(s)
      冨永航平、西川雷羅、山口陽子、永田喜三郎、大木理恵子
    • Organizer
      第39回日本分子生物学会集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-12-02
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒト培養表皮を用いた紫外線照射によるビタミンCの細胞傷害抑制効果2016

    • Author(s)
      河島早紀、永田喜三郎、佐藤安訓、吉田雅幸、石神昭人
    • Organizer
      第39回日本分子生物学会集会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] The role of S100 A8 and A9 proteins in inflammatory responses induced by necrotic cells.2015

    • Author(s)
      市原理恵、小林芳郎、永田喜三郎
    • Organizer
      第44回日本免疫学会
    • Place of Presentation
      札幌コンベンションセンター (北海道札幌市)
    • Year and Date
      2015-11-20
    • Related Report
      2015 Research-status Report
  • [Presentation] The mechanism for β-glucan-mediated inhibition of phagocytosis of apoptotic cells by macrophages.2015

    • Author(s)
      平野哲也、永田喜三郎、小林芳郎
    • Organizer
      第44回日本免疫学会
    • Place of Presentation
      札幌コンベンションセンター (北海道札幌市)
    • Year and Date
      2015-11-19
    • Related Report
      2015 Research-status Report
  • [Presentation] Neutrophil infiltration is essential for gastric mucosal injury in mice with water-immersion stress.2015

    • Author(s)
      近藤嘉高、永田喜三郎、小林芳郎
    • Organizer
      第44回日本免疫学会
    • Place of Presentation
      札幌コンベンションセンター (北海道札幌市)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report

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

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