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Role of the macrophages in non-alcoholic steatohepatitis and impaired glucose tolerance

Research Project

Project/Area Number 25460508
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionNational Defense Medical College

Principal Investigator

Nakashima Hiroyuki  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, その他部局等, 助教 (10574064)

Co-Investigator(Kenkyū-buntansha) SEKI Shuhji  防衛医科大学校, その他部局等, 教授 (80531392)
KINOSHITA Manabu  防衛医科大学校, その他部局等, 准教授 (70531391)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsKupffer cells / 肝再生 / Kupffer細胞 / マクロファージ / 四塩化炭素
Outline of Final Research Achievements

Mouse liver Kupffer cells are classified into two subsets, recruiting CD11b(+) cells with potent cytokine producing capacity and resident CD68(+) cells with strong phagocytic activity. The former population induces hepatocyte apoptosis in experimental hepatitis models. On the contrary, these cells accelerate hepatocyte regeneration after partial hepatectomy. In Non-Alcoholic Steatohepatitis model, this cell population is strongly activated and induces chronic hepatocyte injury which in turn induces hepatic fibrosis and cirrhosis. On the other hand, the latter population expresses PPAR-γ and LXR which are indispensable in glucose and cholesterol metabolism. This result suggests the cell population exerts significant role in energy metabolism.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (18 results)

All 2016 2015 2014 2013

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (13 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Mouse CD11b+Kupffer Cells Recruited from Bone Marrow Accelerate Liver Regeneration after Partial Hepatectomy2015

    • Author(s)
      Nakashima, H. Kinoshita, M. Seki, S.
    • Journal Title

      PLoS One

      Volume: 10 Issue: 9 Pages: e0136774-e0136774

    • DOI

      10.1371/journal.pone.0136774

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Resveratrol increases CD68+ Kupffer cells colocalized with adipose differentiation-related protein and ameliorates high-fat-diet-induced fatty liver in mice.2015

    • Author(s)
      Nishikawa K, Iwaya K, Kinoshita M, Fujiwara Y, Akao M, Sonoda M, Thiruppathi S, Suzuki T, Hiroi S, Seki S, Sakamoto T.
    • Journal Title

      Mol Nutr Food Res

      Volume: 12 Issue: 6 Pages: 564-564

    • DOI

      10.1002/mnfr.201400564

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Fibroblast Growth Factor-5 Participates in the Progression of Hepatic Fibrosis2014

    • Author(s)
      Hiromi Hanaka, Hiroyuki Nakashima, Shuhji Seki
    • Journal Title

      Experimental Animals

      Volume: 63 Issue: 1 Pages: 85-92

    • DOI

      10.1538/expanim.63.85

    • NAID

      130003391608

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2014 Research-status Report
  • [Journal Article] Involvement of the TNF and FasL produced by CD11b Kupffer cells/macrophages in CCl4-induced acute hepatic injury.2014

    • Author(s)
      Sato A, Nakashima H, Nakashima M, Ikarashi M, Nishiyama K, Kinoshita M, Seki S
    • Journal Title

      PLoS ONE

      Volume: 9 Issue: 3 Pages: e92515-e92515

    • DOI

      10.1371/journal.pone.0092515

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distinct development and functions of resident and recruited liver Kupffer cells/macrophages.2013

    • Author(s)
      Ikarashi M, Nakashima H, Kinoshita M, Sato A, Nakashima M, Miyazaki H, Nishiyama K, Yamamoto J, Seki S.
    • Journal Title

      J. Leukocyte. Biol.

      Volume: 94 Issue: 6 Pages: 1325-1336

    • DOI

      10.1189/jlb.0313144

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 加齢に伴う自然免疫機構の低下とピオグリタゾン投与による増強2016

    • Author(s)
      Nakashima, H. Kinoshita, M. Seki, S.
    • Organizer
      第89回日本細菌学会総会
    • Place of Presentation
      大阪 日本
    • Year and Date
      2016-03-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] Decreased innate immunity in aged mice and improvemet by pioglitazone pretreatment2015

    • Author(s)
      Nakashima, H. Kinoshita, M. Seki, S.
    • Organizer
      第44回日本免疫学会
    • Place of Presentation
      札幌 日本
    • Year and Date
      2015-12-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] Mouse CD11b+Kupffer cells recruited from bone marrow accelerate liver regeneration after partial hepatectomy2015

    • Author(s)
      Nakashima, H. Kinoshita, M. Seki, S.
    • Organizer
      Liver meeting 2015 AASLD
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2015-11-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Fibroblast growth factor 5欠損マウスは高脂肪食によりCD11b陽性Kupffer細胞を活性化させ脂肪性肝炎を発症する2015

    • Author(s)
      Nakashima, H. Kinoshita, M. Seki, S.
    • Organizer
      第51回日本肝臓学会総会
    • Place of Presentation
      熊本 日本
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] Activated CD11b+ Kupffer cells/macrophages play the pivotal role in diet induced steatohepatitis in fibroblast growth factor 5 deficient mice2014

    • Author(s)
      Hiroyuki Nakashima, Manabu Kinoshita, Shuhji Seki
    • Organizer
      日本免疫学会総会
    • Place of Presentation
      京都
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Research-status Report
  • [Presentation] Liver X receptor modulates innate immune response in hepatic mononuclear cells2014

    • Author(s)
      Endo-Umeda Kaori, Hiroyuki Nakashima, Shuhji Seki
    • Organizer
      日本免疫学会総会
    • Place of Presentation
      京都
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Research-status Report
  • [Presentation] In vivo endotoxin tolerance alters Kupffer cell phenotype and drastically enhances their bacterial killing2014

    • Author(s)
      Manabu Kinoshita, Hiroyuki Nakashima, Shuhji Seki
    • Organizer
      日本免疫学会総会
    • Place of Presentation
      京都
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Research-status Report
  • [Presentation] Involvement of the TNF and FasL produced by CD11b Kupffer cells/macrophages in CCl4-induced acute hepatic injury2014

    • Author(s)
      Hiroyuki Nakashima, Atsushi Sato, Manabu Kinoshita, Shuhji Seki
    • Organizer
      アメリカ肝臓学会
    • Place of Presentation
      アメリカ ボストン
    • Year and Date
      2014-11-07 – 2014-11-11
    • Related Report
      2014 Research-status Report
  • [Presentation] マウスおよびヒト肝Kupffer細胞/マクロファージの表面抗原、発生分化、機能による包括的分類の新規確立2014

    • Author(s)
      Masami Ikarashi, Hiroyuki Nakashima, Manabu Kinoshita, Shuhji Seki
    • Organizer
      日本肝臓学会総会
    • Place of Presentation
      東京
    • Year and Date
      2014-05-29 – 2014-05-30
    • Related Report
      2014 Research-status Report
  • [Presentation] Activation of CD11b+ Kupffer cells/macrophages as a common cause for exacerbation of TNF/ Fas-ligand-dependent hepatitis in hypercholesterolemic mice2013

    • Author(s)
      Hiroyuki Nakashima, Manabu Kinoshita, Shuhji Seki
    • Organizer
      国際免疫学会議
    • Place of Presentation
      イタリア ミラノ
    • Related Report
      2013 Research-status Report
  • [Presentation] CD11b+ Kupffer cells/macrophages accelarates liver regeneration after partial hepatectomy2013

    • Author(s)
      Kiyoshi Nishiyama, Hiroyuki Nakashima, Manabu Kinoshita, Shuhji Seki
    • Organizer
      日本免疫学会
    • Place of Presentation
      千葉 幕張
    • Related Report
      2013 Research-status Report
  • [Presentation] Glucocorticoid receptor-dependent immunomodulatory effect of ursodeoxycholic acid and on liver lymphocytes in mice2013

    • Author(s)
      Manabu Kinoshita, Hiroyuki Nakashima, Shuhji Seki
    • Organizer
      日本免疫学会
    • Place of Presentation
      千葉 幕張
    • Related Report
      2013 Research-status Report
  • [Presentation] Distinct development and function of resident and recruited liver Kupffer cells / macrophages2013

    • Author(s)
      Masami Ikarashi, Hiroyuki Nakashima, Manabu Kinoshita, Shuhji Seki
    • Organizer
      日本免疫学会
    • Place of Presentation
      千葉 幕張
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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