• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The analysis of inflammatory cascade between antigen specific CTLs and liver injury using hepatitis model

Research Project

Project/Area Number 20390203
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionTokyo Metropolitan Organization for Medical Research

Principal Investigator

KIMURA Kiminori  Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 研究員 (70397339)

Co-Investigator(Kenkyū-buntansha) KAKIMI Kazuhiro  東京大学, 医学部附属病院, 特任准教授 (80273358)
NAGAKI Masahito  岐阜大学, 医学部附属病院, 臨床教授 (30293559)
SAIO Masanao  岐阜大学, 医学系研究科, 准教授 (40242721)
KURACHI Makoto  東京大学, 医学系研究科, 助教 (00396722)
UEHA Satoshi  東京大学, 医学系研究科, 特任助教 (00447385)
Co-Investigator(Renkei-kenkyūsha) MATSUSHIMA Kouji  東京大学, 医学系研究科, 教授 (50222427)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2010: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2008: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Keywords肝臓学 / 免疫 / B型肝炎ウイルス / CTL / ケモカイン / 肝障害 / 接着因子 / CD44
Research Abstract

There are many uncertain points for regarding with leukocytes movement in the liver, especially interaction between liver sinus endothelial cells (LSECs) and cytotoxic T lymphocytes (CTLs). We examined role of CD44 for these interaction using hepatitis model. CTLs were administered into Hepatitis B virus transgenic mice (HBVTg) mice and HBVTgxCD44 knock out (KO) mice, and alanine aminotransferase activity, number of intrahepatic leukocytes, cytokine and chemokine mRNA level were examined. To determine the number and distribution of CTLs in the liver CFSE-labeled CTLs was administered into HBVTg with or without CD44 mice. sALT activity increased since 12 h though it had declined to 4 h in the CD44KOxHBVTg mice after CTLs injection. Similarly, the levels of Tumor necrosis factor (TNF) a, Interferon (IFN) g, Macrophage inflammatory protein (MIP)-2 mRNAs reduced in 4 h though it had been increased since 12 h in the CD44KOxHBVTg mice. The number of apoptotic hepatocytes increased intentionally at 24 h in the CD44KOxHBVTg livers, and it thought to be due to lower activity of initial nuclear factor kappaB (NF-kB). Although the number of CTLs exhibited lower at 4 h in the CD44KOxHBVTg livers the difference of Intercellular adhesion molecule (ICAM)-1 and CD86 expression on LSECs was not detected. CD44 on LSECs exerts important roles for CTLs migration into the hepatocytes. However, since CD44 deficient state was exacerbate hepatic injury, attention is necessary for hepatitis treatment as CD44 target therapy.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (52 results)

All 2011 2010 2009 2008 2007

All Journal Article (30 results) (of which Peer Reviewed: 30 results) Presentation (22 results)

  • [Journal Article] An experimental mouse model for hepatitis C virus.2011

    • Author(s)
      Kimura K, Kohara M
    • Journal Title

      Exp.Animal. 60(2)

      Pages: 93-100

    • NAID

      10029550066

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of interleukin-18 in intrahepatic inflammatory cells recruitment in acute liver injury.2011

    • Author(s)
      Kimura K, Sekiguchi S, Hayashi S, Hayashi y, Hishima T, Nagaki M, Kohara M
    • Journal Title

      Journal of Leukocyte Biology 89(3)

      Pages: 433-42

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Acid sphingomyelinase regulates glucose and lipid metabolism in hepatocytes through AKT activation and AMP-activated protein kinase suppression.2011

    • Author(s)
      Osawa Y, Seki E, Kodama Y, Suetsugu A, Miura K, Adachi M, Ito H, Shiratori Y, Banno Y, Olefsky JM, Nagaki M, Moriwaki H, Brenner DA, Seishima M
    • Journal Title

      FASEB J. 25(4)

      Pages: 1133-44

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Is there a delayed gastric emptying of patients with early-stage, untreated Parkinson's disease? An analysis using the 13C-acetate breath test.2011

    • Author(s)
      Tanaka Y, Kato T, Nishida H, Yamada M, Koumura A, Sakurai T, Hayashi Y, Kimura A, Hozumi I, Araki H, Murase M, Nagaki M, Moriwaki H, Inuzuka T
    • Journal Title

      J Neurol. 258(3)

      Pages: 421-6

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] An experimental mouse model for hepatitis C virus.2011

    • Author(s)
      Kimura K, Kohara M.
    • Journal Title

      Exp.Animal.

      Volume: 60(2) Pages: 93-100

    • NAID

      10029550066

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] No relapse of neuromyelitis optica during secondary low B lymphocytes.2010

    • Author(s)
      Tanaka S, Kimura K, Kawachi t, Inuzuka T
    • Journal Title

      Neurology 75(19)

      Pages: 1745-7

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Roles of CD44 in chemical-induced liver injury.2010

    • Author(s)
      Kimura K, Hayashi S, Nagaki M
    • Journal Title

      Curr Opin Drug Discov Devel. 13(1)(Review)

      Pages: 96-103

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of acid sphingomyelinase of Kupffer cells in cholestatic liver injury in mice.2010

    • Author(s)
      Osawa Y, Seki E, Adachi M, Suetsugu A, Ito H, Moriwaki H, Seishima M, Nagaki M
    • Journal Title

      Hepatology. 51(1)

      Pages: 237-45

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bone marrow graft-versus-host disease : early destruction of hematopoietic niche after MHC-mismatched hematopoietic stem cell transplantation.2010

    • Author(s)
      Shono Y, Ueha S, Wang Y, Abe J, Kurachi M, Matsuno Y, Sugiyama T, Nagasawa T, Imamura M, Matsushima K
    • Journal Title

      Blood. 115(26)

      Pages: 5401-11

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] No relapse of neuromyelitis optica during secondary low B lymphocytes.2010

    • Author(s)
      Tanaka S, Kimura K, et al.
    • Journal Title

      Neurology

      Volume: 75(19) Pages: 1745-1747

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of interleukin-18 in intrahepatic inflammatory cells recruitment in acute liver injury.2010

    • Author(s)
      Kimura k, Sekiguchi S, et al.
    • Journal Title

      Journal of Leukocyte Biology

      Volume: 89(3) Pages: 433-442

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles of CD44 in chemical-induced liver injury2010

    • Author(s)
      Kimura, et al.
    • Journal Title

      Current Opinion in Drug Discovery & Development 13(1)

      Pages: 96-103

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Extended treatment duration of peginterferon-alpha2b plus ribavirin for 72 and 96 weeks in hepatitis C genotype 1-infected late responders.2009

    • Author(s)
      Nagaki M, Shimizu M, Sugihara JI, Tomita E, Sano C, Naiki T, Kimura K, Amano K, Sakai T, Ninomiya M, Kojima T, Katsumura N, Fujimoto M, Moriwaki H
    • Journal Title

      Aliment Pharmacol Ther. 30(4)

      Pages: 343-51

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pathological role of CD44 on NKT cells in carbon tetrachloride-mediated liver injury.2009

    • Author(s)
      Kimura K, Nagaki M, Matsura T, Moriwaki H, Kakimi K
    • Journal Title

      Hepatol Res 39(1)

      Pages: 93-105

    • NAID

      10025324211

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of CD44 blocking for CTL-induced acute liver injury in the hepatitis B virus transgenic mice.2009

    • Author(s)
      Kimura K, Nagaki M, Saio M, Moriwaki M, Kakimi K
    • Journal Title

      J gastroenterology 44(3)

      Pages: 218-27

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Extracellular matrix is required for the survival and differentiation of transplanted hepatic progenitor cells.2009

    • Author(s)
      Tsukada Y, Nagaki M, Suetsugu A, Osawa Y, Moriwaki H
    • Journal Title

      Biochem Biophys Res Commun. 381(4)

      Pages: 733-7

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Extended treatment duration of peginterferon-alpha2b plus ribavirin for 72 and 96 weeks in hepatitis C genotype 1-infected late responders2009

    • Author(s)
      Nagaki, et al.
    • Journal Title

      Aliment Pharmacol Ther. 15;30(4)

      Pages: 343-351

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathological role of CD44 on NKT cells in carbon tetrachloride-mediated liver injury2009

    • Author(s)
      Kimura, et al.
    • Journal Title

      Hepatol Res 39(1)

      Pages: 93-105

    • NAID

      10025324211

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of CD44 blocking for CTL-induced acute liver injury in the hepatitis B virus transgenic mice2009

    • Author(s)
      Kimura, et al.
    • Journal Title

      J gastroenterology 44(3)

      Pages: 218-227

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A case of polymyositis associated with peg interferon alpha-2b and ribavirin therapy for chronic hepatitis C2009

    • Author(s)
      Okuma, et al.
    • Journal Title

      Clinical J Gastorol 2(5)

      Pages: 346-350

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of CD44 blocking for CTL-induced acute liver injury in the hepatitis B virus transge2009

    • Author(s)
      Kimura k, et al.
    • Journal Title

      Journal of gastroenterology 44(3)

      Pages: 218-227

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathological role of CD44 on NKT cells in carbon tetrachloride-mediated liver injury2009

    • Author(s)
      Kimura k, et al.
    • Journal Title

      Hepatology Research 39(1)

      Pages: 93-105

    • NAID

      10025324211

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Memory Th1 cell augments tumor-specific CTL following transcutaneous peptide immunization.2008

    • Author(s)
      Hosoi A, Takeda Y, Furuichi Y, Kurachi M, Kimura K, Maekawa R, Takatsu K, Kakimi K
    • Journal Title

      Cancer Res. 68(10)

      Pages: 3941-9

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dendritic cell vaccine with mRNA targeted to the proteasome by polyubiquitination.2008

    • Author(s)
      Hosoi A, Takeda Y, Sakuta K, Ueha S, Kurachi M, Kimura K, Maekawa R, Kakimi K
    • Journal Title

      Biochem Biophys Res Commun. 371(2)

      Pages: 242-6

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of CD44 in Hepatotoxin mediated liver injury2008

    • Author(s)
      Kimura K, Nagaki M, Kakimi K, Saio M, Saeki T, Okuda Y, Kuwata K, Moriwaki H
    • Journal Title

      J hepatol 48(6)

      Pages: 952-61

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice.2008

    • Author(s)
      Sawanobori Y, Ueha S, Kurachi M, Shimaoka T, Talmadge JE, Abe J, Shono Y, Kitabatake M, Kakimi K, Mukaida N, Matsushima K
    • Journal Title

      Blood. 111(12)

      Pages: 5457-66

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Memory Th1 cells augment tumor-specific CTL following transcutaneous peptide immunizat2008

    • Author(s)
      Hosoi A, et al.
    • Journal Title

      Cancer Research 15;68(10)

      Pages: 3941-3949

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dendritic cell vaccine with mRNA targeted to the proteasome by polyubiquitination2008

    • Author(s)
      Hosoi A, et al.
    • Journal Title

      Biochem Biophys Res Commun. Jun 27;371(2)

      Pages: 242-246

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of CD44 in hepatotoxin-mediated liver injury2008

    • Author(s)
      Kimura K, et al.
    • Journal Title

      Journal of Heputology Jun;48(6)

      Pages: 952-961

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Significant effect of hepatitis C virus specific CTLs on viral clearance in patients with type C chronic hepatitis treated with antiviral agents.2007

    • Author(s)
      Satake S, Nagaki M, Kimura K, Naiki T, Hayashi H, Sugihara J, Tomita E, Moriwaki H
    • Journal Title

      Hepatol Res.

    • NAID

      10024148453

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Presentation] Hepatitis C virus-mediated pathogenesis is dependent on inflammatory cytokines irrespective of the HCV protein level2011

    • Author(s)
      Kiminori Kimura, Michinori Kohara, et al
    • Organizer
      keystone symposia
    • Place of Presentation
      Calgary
    • Year and Date
      2011-02-01
    • Related Report
      2010 Final Research Report
  • [Presentation] Hepatitis C virus-mediated pathogenesis is dependent on inflammatory cytokines irrespective of the HCV protein level2011

    • Author(s)
      Kiminori Kimura
    • Organizer
      keystone symposia
    • Place of Presentation
      Calgary(CANADA)
    • Year and Date
      2011-02-01
    • Related Report
      2010 Annual Research Report
  • [Presentation] HCV感染による慢性肝炎の病態形成と炎症性サイトカインの関与2011

    • Author(s)
      木村公則、小原道法
    • Organizer
      日本肝臓学会総会シンポジウム
    • Place of Presentation
      東京
    • Related Report
      2010 Final Research Report
  • [Presentation] Hepatitis C virus-mediated pathogenesis is dependent on inflammatory cytokines irrespective of the HCV protein level2010

    • Author(s)
      Kiminori Kimura
    • Organizer
      AASLD
    • Place of Presentation
      Boston(USA)
    • Year and Date
      2010-12-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] Critical role of IL-18 for intrahepatic inflammatory cell recruitment in activated macrophages mediated liver injury2010

    • Author(s)
      Kiminori Kimura
    • Organizer
      AASLD
    • Place of Presentation
      Boston(USA)
    • Year and Date
      2010-12-01
    • Related Report
      2010 Annual Research Report
  • [Presentation] Hepatitis C virus-mediated pathogenesis is dependent on inflammatory cytokines irrespective of the HCV protein level2010

    • Author(s)
      Kiminori Kimura
    • Organizer
      HCV meeting
    • Place of Presentation
      Yokohama(JAPAN)
    • Year and Date
      2010-09-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Role of CD44 in chemical induced liver injury2010

    • Author(s)
      Kiminori Kimura, Masahito Nagaki
    • Organizer
      EASL topic conference
    • Place of Presentation
      Amsterdam
    • Year and Date
      2010-02-18
    • Related Report
      2010 Final Research Report
  • [Presentation] Hepatitis C virus-mediated pathogenesis is dependent on inflammatory cytokines irrespective of the HCV protein level2010

    • Author(s)
      Kiminori Kimura
    • Organizer
      EASL topic conference
    • Place of Presentation
      Amsterdam(オランダ)
    • Year and Date
      2010-02-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] Critical role of IL-18 for intrahepatic inflammatory cell recruitment in activated macrophages mediated liver injury2010

    • Author(s)
      Kiminori Kimura, Satoshi Sekiguchi, et al
    • Organizer
      AASLD
    • Place of Presentation
      Boston
    • Related Report
      2010 Final Research Report
  • [Presentation] Hepatitis C virus-mediated pathogenesis is dependent on inflammatory cytokines irrespective of the HCV protein level2010

    • Author(s)
      Kiminori Kimura, Michinori Kohara, et al
    • Organizer
      AASLD
    • Place of Presentation
      Boston
    • Related Report
      2010 Final Research Report
  • [Presentation] Hepatitis C virus-mediated pathogenesis is dependent on inflammatory cytokines irrespective of the HCV protein level2010

    • Author(s)
      Kiminori Kimura, Michinori Kohara, et al
    • Organizer
      HCV meeting
    • Place of Presentation
      Yokohama
    • Related Report
      2010 Final Research Report
  • [Presentation] C型慢性肝炎に対する遺伝子組換えワクチニアウイルスによる新たな治療戦略2010

    • Author(s)
      木村公則、小原道法
    • Organizer
      日本肝臓学会大会ワークショップ
    • Place of Presentation
      横浜
    • Related Report
      2010 Final Research Report
  • [Presentation] Resolution of HCV chronic hepatitis with immunotherapy using Hepatitis C virus recombinant vaccinia virus in persistent infection model mice2009

    • Author(s)
      関口敏, et al.
    • Organizer
      AASLD's 60th Annual Meeting
    • Place of Presentation
      ボストン・アメリカ
    • Year and Date
      2009-11-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] HCV遺伝子組換えワクチニアウイルスによる免疫治療2009

    • Author(s)
      関口敏
    • Organizer
      第57回日本ウイルス学会学術集会
    • Place of Presentation
      東京都・都市センターホテル
    • Year and Date
      2009-10-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] 抗CD40抗体を用いた肝障害モデルにおけるNKT細胞とマクロファージの相互作用2009

    • Author(s)
      木村公則
    • Organizer
      第45回日本肝臓学会総会
    • Place of Presentation
      兵庫県・神戸ポートピアホテル、神戸国際展示場
    • Year and Date
      2009-06-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] B型急性肝炎モデルにおけるThioredoxin-1の関与2008

    • Author(s)
      木村公則、永木正仁
    • Organizer
      日本肝臓学会東部会シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2008-12-04
    • Related Report
      2010 Final Research Report
  • [Presentation] B型急性肝炎モデルにおける Thioredoxin-1 の関与2008

    • Author(s)
      木村公則
    • Organizer
      日本肝臓学会東部会
    • Place of Presentation
      東京
    • Year and Date
      2008-12-04
    • Related Report
      2008 Annual Research Report
  • [Presentation] Interaction of CTLs and CD44 in acute hepatitis model using hepatitis B virus transgenic mice2008

    • Author(s)
      Kiminori Kimura, Michinori Kohara, et al
    • Organizer
      AASLD
    • Place of Presentation
      San Francisco
    • Year and Date
      2008-11-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Interaction of CTLs and CD44 in acute hepatitis model using hepatitis B virus transgenic m2008

    • Author(s)
      Kiminori Kimura
    • Organizer
      The annual meeting of the american association for the study of liver diseas
    • Place of Presentation
      サンフランシスコ
    • Year and Date
      2008-11-02
    • Related Report
      2008 Annual Research Report
  • [Presentation] B型肝炎治療における自然免疫制御の有用性2008

    • Author(s)
      木村公則、永木正仁
    • Organizer
      日本肝臓学会シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2008-10-02
    • Related Report
      2010 Final Research Report
  • [Presentation] B型肝炎治療における自然免疫制御の有用性2008

    • Author(s)
      木村公則
    • Organizer
      日本肝臓学会大会
    • Place of Presentation
      東京
    • Year and Date
      2008-10-02
    • Related Report
      2008 Annual Research Report
  • [Presentation] B型肝炎トランスジェニックマウスを用いた急性肝炎モデルにおけるCTLとCD44の相互作用2008

    • Author(s)
      木村公則
    • Organizer
      日本肝臓学会総会
    • Place of Presentation
      松山市
    • Year and Date
      2008-06-06
    • Related Report
      2008 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi