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Elucidation for Histone induced cell death in sepsis

Research Project

Project/Area Number 16K15681
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Anesthesiology
Research InstitutionToho University

Principal Investigator

NAKABAYASHI Osamu  東邦大学, 医学部, 助教 (50328613)

Co-Investigator(Kenkyū-buntansha) 山崎 創  東邦大学, 医学部, 准教授 (70315084)
中野 裕康  東邦大学, 医学部, 教授 (70276476)
Co-Investigator(Renkei-kenkyūsha) NAKANO Hiroyasu  東邦大学, 医学部, 教授 (70276476)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsHistone / sepsis / cell death / gene trap / ヒストン / 細胞死 / 敗血症 / Gene-trap / CRISPR/Cas9 / CRISPR-Cas9
Outline of Final Research Achievements

Circulating histones are major mediators of sepsis and cytotoxic to vascular endothelium. For analyzing cytotoxic mechanism of histones, we constructed a haploid genetic screen system using HAP1 cells. Infection efficiency of gene-trap vector to HAP1 cells was 32%, it revealed that high frequency integration was occurred in gene structures. We treated gene-trapped HAP1 cells with histones, surviving cells were treated with histones again.
We could not find a mediator gene of histone toxicity, but histones have possibilities medical targets for sepsis.

Report

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

    (39 results)

All 2018 2017 2016

All Journal Article (9 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 8 results,  Acknowledgement Compliant: 5 results) Presentation (30 results) (of which Int'l Joint Research: 5 results,  Invited: 4 results)

  • [Journal Article] Blockade of TNF receptor superfamily 1 (TNFR1)-dependent and TNFR1-independent cell death is crucial for normal epidermal differentiation2018

    • Author(s)
      Piao Xuehua、Miura Ryosuke、Miyake Sanae、Komazawa-Sakon Sachiko、Koike Masato、Shindo Ryodai、Takeda Junji、Hasegawa Akito、Abe Riichiro、Nishiyama Chiharu、Mikami Tetsuo、Yagita Hideo、Uchiyama Yasuo、Nakano Hiroyasu
    • Journal Title

      Journal of Allergy and Clinical Immunology

      Volume: - Issue: 1 Pages: 213-228.e10

    • DOI

      10.1016/j.jaci.2018.02.043

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The AP-1 transcription factor JunB is required for Th17 cell differentiation2017

    • Author(s)
      Yamazaki Soh、Tanaka Yoshihiko、Araki Hiromitsu、Kohda Akira、Sanematsu Fumiyuki、Arasaki Tomoko、Duan Xuefeng、Miura Fumihito、Katagiri Takaharu、Shindo Ryodai、Nakano Hiroyasu、Ito Takashi、Fukui Yoshinori、Endo Shogo、Sumimoto Hideki
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 17402-17402

    • DOI

      10.1038/s41598-017-17597-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 肝炎の制御における骨髄由来細胞の役割2017

    • Author(s)
      山﨑 創, 朴 雪花, 中野 裕康
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 68(5) Pages: 455-462

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Depletion of myeloid cells exacerbates hepatitis and induces an aberrant increase in histone H3 in mouse serum2017

    • Author(s)
      Piao, X. Yamazaki, S. Komazawa-Sakon, S. Miyake, S. Nakabayashi, O. Kurosawa, T. Mikami, T. Tanaka, M. Van Rooijen, N. Ohmuraya, M. Oikawa, A. Kojima, Y. Kakuta, S. Uchiyama, Y. Tanaka, M. Nakano, H.
    • Journal Title

      Hepatology

      Volume: 65 Issue: 1 Pages: 237-252

    • DOI

      10.1002/hep.28878

    • NAID

      120006528815

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Critical contribution of nuclear factor erythroid 2-related factor 2 (NRF2) to electrophile-induced Interleukin-11 production.2017

    • Author(s)
      Nishina T, Deguchi Y, Miura R, Yamazaki S, Shinkai Y, Kojima Y, Okumura K, Kumagai Y, Nakano H.
    • Journal Title

      Journal of Biological Chemistry

      Volume: 292 Issue: 1 Pages: 205-216

    • DOI

      10.1074/jbc.m116.744755

    • NAID

      120007135104

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] HTLV-1 Tax Induces Formation of the Active Macromolecular IKK Complex by Generating Lys63- and Met1-Linked Hybrid Polyubiquitin Chains.2017

    • Author(s)
      Shibata Y, Tokunaga F, Goto E, Komatsu G, Gohda J, Saeki Y, Tanaka K, Takahashi H, Sawasaki T, Inoue S, Oshiumi H, Seya T, Nakano H, Tanaka Y, Iwai K, Inoue J.
    • Journal Title

      PLoS Pathog

      Volume: 13:e1006162 Pages: 6162-6163

    • NAID

      120006825915

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Short form FLICE-inhibitory protein promotes TNFalpha-induced necroptosis in fibroblasts derived from CFLARs transgenic mice2016

    • Author(s)
      Shindo, R. Yamazaki, S. Ohmuraya, M. Araki, K. Nakano, H.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 480 Issue: 1 Pages: 23-28

    • DOI

      10.1016/j.bbrc.2016.10.015

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Novel method to rescue a lethal phenotype through integration of target gene onto the X-chromosome2016

    • Author(s)
      Sakata, K. Araki, K. Nakano, H. Nishina, T. Komazawa-Sakon, S. Murai, S. Lee, G. E. Hashimoto, D. Suzuki, C. Uchiyama, Y. Notohara, K. Gukovskaya, A. S. Gukovsky, I. Yamamura, K. I. Baba, H. Ohmuraya, M.
    • Journal Title

      Sci Rep

      Volume: 6 Issue: 1 Pages: 37200-37200

    • DOI

      10.1038/srep37200

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The nuclear protein IκBζ forms a transcriptionally active complex with nuclear factor-κB (NF-κB) p50 and Lcn2 promoter via the N- and C-terminal ankyrin repeat motifs2016

    • Author(s)
      Kohda A, Yamazaki S, Sumimoto H.
    • Journal Title

      J. Biol. Chem.

      Volume: 291 Issue: 39 Pages: 20739-20752

    • DOI

      10.1074/jbc.m116.719302

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Short form FLICE-inhibitory protein promotes TNFα-induced necroptosis in fibroblasts derived from CFLARs transgenic mice2017

    • Author(s)
      ◎Ryodai Shindo, Soh Yamazakia, Masaki Ohmuraya, Kimi Araki, Hiroyasu Nakano.
    • Organizer
      Keystone Symposia on Molecular and Cellular Biology
    • Place of Presentation
      Keystone, Colorado, USA
    • Year and Date
      2017-02-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of Interleukin-11-producing cells in a colitis-associated cancer model using IL-11 reporter mice2017

    • Author(s)
      ◎Takashi Nishina, Yutaka Deguchi, Eri Nakamura, Yuko Kojima, Norihiro Tada, Hiroyasu Nakano
    • Organizer
      Keystone Symposia on Molecular and Cellular Biology
    • Place of Presentation
      Keystone, Colorado, USA
    • Year and Date
      2017-02-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Deletion of Cflar in the epidermis results in TNFR1-dependent and -independent lethal dermatitis.2017

    • Author(s)
      ◎三浦亮介、朴雪花、三宅早苗、駒沢幸子、小池正人、内山安男、中野裕康
    • Organizer
      細胞競合・ダイイングコード合同若手ワークショップ
    • Place of Presentation
      ホテルコスモスクエア国際交流センター(大阪府・大阪市)
    • Year and Date
      2017-01-17
    • Related Report
      2016 Research-status Report
  • [Presentation] Short form FLICE-inhibitory protein promotes TNFα-induced necroptosis in fibroblasts derived from CFLARs transgenic mice2017

    • Author(s)
      ◎進藤綾大、山崎創、大村谷昌樹、荒木喜美、中野裕康
    • Organizer
      細胞競合・ダイイングコード合同若手ワークショップ
    • Place of Presentation
      ホテルコスモスクエア国際交流センター(大阪府・大阪市)
    • Year and Date
      2017-01-17
    • Related Report
      2016 Research-status Report
  • [Presentation] Intestinal epithelial cell (IEC)-specific Cflar-deficient mice spontaneously develop TNFR1-independent ileitis2017

    • Author(s)
      ◎片桐翔治、朴雪花、中野 裕康
    • Organizer
      細胞競合・ダイイングコード合同若手ワークショップ
    • Place of Presentation
      ホテルコスモスクエア国際交流センター(大阪府・大阪市)
    • Year and Date
      2017-01-17
    • Related Report
      2016 Research-status Report
  • [Presentation] RORγt-positive cells mediate RIPK3- and MLKL-dependent lethal ileitis in neonatal mice2017

    • Author(s)
      Ryodai Shindo、Soh Yamazaki、Hiroyasu Nakano
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 計画的ネクローシスをモニターするFRETバイオセンサーによるDAMPs放出メカニズムの解明2017

    • Author(s)
      村井 晋、 山口 良文、白崎 善隆、進藤 綾大、中林 修、三浦 亮介、冨田 太一郎、赤羽 悟美、三浦 正幸、中野 裕康
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] MIND BOMB-2はcFLIPLをユビキチン化することで細胞死を抑制する2017

    • Author(s)
      中林 修、 高橋 宏隆、澤崎 達也、吉田 雪子、 佐伯 泰、中野 裕康
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] CFLIPはTNFR1依存的な致死的皮膚炎とTNFR1非依存的な表皮分化障害を防ぐ2017

    • Author(s)
      三浦 亮介、朴 雪花、三宅 早苗、駒沢 幸子、小池 正人、進藤 綾大、内山 安男、中野 裕康
    • Organizer
      第40回日本分子生物学会年会 第90回日本生化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ネクロプトーシスによる生体応答制御2017

    • Author(s)
      中野 裕康
    • Organizer
      第40回日本分子生物学会年会 第90回日本生化学会大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] インターロイキン11の産生制御と産生細胞の同定2017

    • Author(s)
      中野 裕康
    • Organizer
      第14回レドックス・ライフイノベーションシンポジウム
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 肝特異的cFLIP低発現マウスを用いた肝障害モデルの解析2017

    • Author(s)
      山﨑 創、朴 雪花、駒澤 幸子、三宅 早苗、中林 修、田中 稔、大村谷 昌樹、及川 彰、角田 宗一郎、内山 安男、 田中 正人, 中野 裕康
    • Organizer
      第26回日本Cell Death学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] cFLIPはTNFR1依存的な致死的皮膚炎とTNFR1非依存的な表皮分化障害を防ぐ2017

    • Author(s)
      三浦 亮介、朴 雪花、三宅 早苗、駒沢 幸子、小池 正人、進藤 綾大、内山 安男、中野 裕康
    • Organizer
      第26回日本Cell Death学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Ⅱ型肺胞上皮細胞障害の障害と再生に関する解析2017

    • Author(s)
      三好 嗣臣、黒澤 武介、仁科 隆史、山崎 創、本間 栄、中野 裕康
    • Organizer
      第26回日本Cell Death学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] RORγt陽性細胞はRIPK3およびMLKL依存性に小腸炎を誘導する2017

    • Author(s)
      進藤 綾大、大村谷 昌樹、駒澤 幸子、三宅 早苗、山﨑 創、仁科 隆史、小西 博之、木山 博資、三上 哲夫、荒木 喜美、中野 裕康
    • Organizer
      第26回日本Cell Death学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] SMARTによるネクロプトーシス進行の継時的解析2017

    • Author(s)
      村井 晋、白崎 善隆、山口 良文、冨田 太一郎、赤羽 悟美、三浦 正幸、中野 裕康
    • Organizer
      第26回日本Cell Death学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 腸上皮特異的cFLIP欠損マウスで見られるTNFR1非依存性腸炎の発症メカニズムの解析2017

    • Author(s)
      片桐 翔治、朴 雪花、進藤 綾大、駒沢 幸子、大村谷 昌樹、中野 裕康
    • Organizer
      第26回日本Cell Death学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 親電子リガンドによるIL-11産生機構とその生体における役割の解明2017

    • Author(s)
      仁科 隆史、出口 裕、三浦 亮介、山﨑 創、新開 泰弘、小島 裕子、奥村 康、熊谷 嘉人、中野 裕康
    • Organizer
      第44回日本毒性学会学術年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] RORγt+ group 3 innate lymphoid cells mediate RIPK3-dependent lethal ileitis2017

    • Author(s)
      Hiroyasu Nakano
    • Organizer
      16th TNF super family meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] The AP-1 transcription factor JunB is essential for development of Th17 cells2017

    • Author(s)
      Soh Yamazaki, Yoshihiko Tanaka, Yoshinori Fukui, Hideki Sumimoto
    • Organizer
      第46回日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 電子顕微鏡を用いたネクロプトーシスの微細構造の解析2016

    • Author(s)
      ◎三宅早苗, 角田宗一郎, 小池正人, 内山安男, 中野裕康
    • Organizer
      第39回日本分子生物学会年会
    • 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] アポトーシス細胞は腸内細菌非依存的にReg3βを産生し腸管の恒常性を維持する2016

    • Author(s)
      ◎進藤綾大、大村谷昌樹、駒澤幸子、三宅早苗、山崎創、仁科隆史、小西博之、木山博資、三上哲夫、荒木喜美、中野裕康
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      東北大学川内北キャンパス(宮城県・仙台市)
    • Year and Date
      2016-09-27
    • Related Report
      2016 Research-status Report
  • [Presentation] 細胞死制御因子cFLIPの肝細胞特異的欠損マウスを用いた肝障害モデルにおけるクッパー細胞および骨髄由来細胞の役割2016

    • Author(s)
      朴 雪花, ◎山﨑 創, 駒澤-左近 幸子, 三宅 早苗, 中林 修, 田中 稔, 大村谷 昌樹, 及川 彰, 角田 宗一郎, 内山 安男, 田中 正人, 中野 裕康
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      東北大学川内北キャンパス(宮城県・仙台市)
    • Year and Date
      2016-09-26
    • Related Report
      2016 Research-status Report
  • [Presentation] 肝細胞死亢進マウスを用いた肝幹細胞増殖因子同定の試み2016

    • Author(s)
      ◎土屋勇一, 田中稔, 鶴崎慎也, 及川彰, 駒澤幸子, 三上哲夫, 中野裕康
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      東北大学川内北キャンパス(宮城県・仙台市)
    • Year and Date
      2016-09-26
    • Related Report
      2016 Research-status Report
  • [Presentation] 肝細胞死亢進マウスモデルを用いた肝再生や炎症制御のメカニズムの解明2016

    • Author(s)
      ◎中野裕康
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      東北大学川内北キャンパス(宮城県・仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 親電子リガンドによるIL-11産生機構とその生体における役割の解明2016

    • Author(s)
      ◎仁科 隆史、出口 裕、三浦 亮介、新開 泰弘、小島 裕子、熊谷 嘉人、中野 裕康
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      東北大学川内北キャンパス(宮城県・仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] ネクロプトーシスをモニターするFRETプローブの開発2016

    • Author(s)
      ◎村井 晋, 山口 良文, 中林 修, 冨田 太一郎, 赤羽 悟美, 三浦 正幸, 中野 裕康
    • Organizer
      第25回 日本Cell Death学会学術集会
    • Place of Presentation
      きゅりあん(東京都・品川区)
    • Year and Date
      2016-09-10
    • Related Report
      2016 Research-status Report
  • [Presentation] CD4+ T cell-intrinsic TRAF5 negatively regulates Th17 cell-dependent experimental autoimmune encephalomyelitis2016

    • Author(s)
      ◎Hiroyuki Nagashima, Yuko Okuyama, Takaya Hayashi, Atsuko Asao, Takeshi Kawabe, Satoshi Yamaki, Hiroyasu Nakano, Michael Croft, Naoto Ishii, Takanori So.
    • Organizer
      第16回国際免疫学会議
    • Place of Presentation
      メルボルン、オーストラリア
    • Year and Date
      2016-08-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] TRAF adaptors limit the IL-6 receptor signaling through an unexpected binding to the signaling transducer receptor gp130.2016

    • Author(s)
      ◎Takanori So, Hiroyuki Nagashima, Yuko Okuyama, Takaya Hayahi, Atsuko Asao, Takeshi Kawabe, Satoshi Yamaki, Hiroyasu Nakano, Michael Croft, Naoto Ishii.
    • Organizer
      第16回国際免疫学会議
    • Place of Presentation
      メルボルン、オーストラリア
    • Year and Date
      2016-08-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 転写因子NF-κBとそのパートナータンパク質IκBζによる転写活性化複合体の形成機構2016

    • Author(s)
      神田 朗、山﨑 創、住本 英樹
    • Organizer
      第27回日本生体防御学会学術総会
    • Place of Presentation
      九州大学病院キャンパス内コラボステーションI視聴覚ホール(福岡県・福岡市)
    • Year and Date
      2016-07-09
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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