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Development of artificial liver support system combining with liver cells and Kuppfer cells.

Research Project

Project/Area Number 23591984
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionUniversity of Yamanashi

Principal Investigator

FUJII Hideki  山梨大学, 医学工学総合研究部, 教授 (30181316)

Co-Investigator(Kenkyū-buntansha) KONO Hiroshi  山梨大学, 医学工学総合研究部, 助教 (40322127)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords肝不全 / 人工肝補助装置 / 肝Kupffer細胞 / GCSF / M-CSF / 新生血管 / IL-17 / 脾臓摘出 / Kupffer細胞 / ノックアウトマウス / 肝再生 / TNF-α / CD4陽性リンパ球 / CLP model / IL-17A / HMGB1 / 肝温虚血再還流モデル / glycyrrhizin
Research Abstract

IL-17A regulates neutrophil-dependent organ injury. The purpose of this study was to determine the role of IL-17A in neutrophil recruitment after ischemia-reperfusion (I/R). Wild-type (WT) and IL-17A knockout (KO) mice were evaluated. In another experiments, recombinant (rm) IL-17A or rmIL-17A/F were administered before I/R. Isolated Kupffer cells were incubated with rmIL-17A and production of TNF-alpha was measured. The extent of liver injury demonstrated similar levels in the acute phase (6 h) in these two models. In contrast, in the subacute phase (20 h), liver injury were significantly reduced in the KO compared with the WT. This reduction in liver injury was associated with suppression of chemokine, adhesion molecule expression and reduction in infiltration of neutrophils into the liver. TNF-alpha production by isolated Kupffer cells increased significantly with rmIL-17A. IL-17A is a key regulator in initiating neutrophil-induced inflammatory responses and hepatic injury.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (28 results)

All 2014 2013 2012 2011 Other

All Journal Article (26 results) (of which Peer Reviewed: 26 results) Remarks (2 results)

  • [Journal Article] Typical fibrolamellar hepatocellular carcinoma in a Japanese boy: report of a case.2014

    • Author(s)
      Matsuda M
    • Journal Title

      Surg Today

      Volume: - Issue: 7 Pages: 1359-1366

    • DOI

      10.1007/s00595-013-0653-y

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Diagnostic criteria for pancreaticobiliary maljunction 20132013

    • Author(s)
      Kamisawa T, Ando H, Hamada Y, Fujii H, Koshinaga T, Urushihara N, Itoi T, Shimada H.
    • Journal Title

      J Hepatobiliary Pancreat Sci.

      Volume: Mar;21(3) Issue: 3 Pages: 159-61

    • DOI

      10.1002/jhbp.57

    • NAID

      130004838889

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Presence of a hypovascular hepatic nodule showing hypointensity on hepatocyte-phase image is a risk factor for hypervascular hepatocellular carcinoma.2013

    • Author(s)
      Ichikawa S, Ichikawa T, Motosugi U, Sano K, Morisaka H, Enomoto N, Matsuda M, Fujii H, Araki T.
    • Journal Title

      J Magn Reson Imaging.

      Volume: 39(2) Issue: 2 Pages: 293-297

    • DOI

      10.1002/jmri.24164

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Macrophage colony-stimulating factor plays a pivotal role in chemically induced hepatocellular carcinoma in mice.2013

    • Author(s)
      Hara M
    • Journal Title

      Hepatol Res

      Volume: Epub ahead of print Issue: 7 Pages: 798-811

    • DOI

      10.1111/hepr.12174

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Extrahepatic bile duct measurement by using transabdominal ultrasound in Japanese adults: multi-center prospective study.2013

    • Author(s)
      Itoi T
    • Journal Title

      J Gastroenterol

      Volume: 48(9) Issue: 9 Pages: 1045-50

    • DOI

      10.1007/s00535-012-0702-0

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The MAPK Pathway Is a Predominant Regulator of HLA-A Expression in Esophageal and Gastric Cancer.2013

    • Author(s)
      Mimura K
    • Journal Title

      J Immunol

      Volume: 191(12) Issue: 12 Pages: 6261-72

    • DOI

      10.4049/jimmunol.1301597

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cervical lymph node dissection for clinically submucosal carcinoma of the thoracic esophagus.2013

    • Author(s)
      Kosugi S
    • Journal Title

      Ann Surg Oncol

      Volume: 20(12) Issue: 12 Pages: 4016-21

    • DOI

      10.1245/s10434-013-3141-0

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Bayesian prediction for liver fibrosis staging: Combined use of elastography and serum fibrosis markers.2013

    • Author(s)
      Motosugi U
    • Journal Title

      Hepatology

      Volume: 58 Issue: 1 Pages: 450-51

    • DOI

      10.1002/hep.26144

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pancreatobiliary reflux in individuals with a normal pancreaticobiliary junction: a prospective multicenter study.2013

    • Author(s)
      Horaguchi J
    • Journal Title

      J Gastroenterol

      Volume: - Issue: 5 Pages: 875-881

    • DOI

      10.1007/s00535-013-0837-7

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Early hepatocellular carci nomas showing isointensity or hyper intensity in gadoxetic Acid-enhance d, hepatocyte-phase magnetic resona nce images2013

    • Author(s)
      Chen N, Motosugi U, Sano K, Ichikaw a T, Nakano M, Morisaka H, Ichikawa S, Matsuda M, Fujii H, Enomoto N, Araki T.
    • Journal Title

      J Comput Assist Tomogr

      Volume: 37 Issue: 3 Pages: 466-469

    • DOI

      10.1097/rct.0b013e3182873799

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Real-time diagnosis of chemically induced hepatocellular carcinoma using a novel mass spectrometry-based technique2013

    • Author(s)
      K. Yoshimura, M. K. Mandal, M . Hara, H. Fujii, L. C. Chen, K. Tanabe , K. Hiraoka and S. Takeda
    • Journal Title

      Analytical Biochemistry

      Volume: 441 Issue: 1 Pages: 32

    • DOI

      10.1016/j.ab.2013.06.017

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Small-cell carcinoma of the breast with squamous differentiation.2013

    • Author(s)
      Kawasaki T
    • Journal Title

      Histopathology

      Volume: 63(5) Issue: 5 Pages: 739-41

    • DOI

      10.1111/his.12201

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-17A plays a pivotal role after partial hepatectomy in mice.2013

    • Author(s)
      Furuya S
    • Journal Title

      J Surg Res

      Volume: 184(2) Issue: 2 Pages: 838-46

    • DOI

      10.1016/j.jss.2013.03.033

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-17A plays a pivotal role in cholestatic liver fibrosis in mice.2013

    • Author(s)
      Hara M
    • Journal Title

      J Surg Res

      Volume: 183(2) Issue: 2 Pages: 574-82

    • DOI

      10.1016/j.jss.2013.03.025

    • Related Report
      2013 Annual Research Report 2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased prevalence of tumor-infiltrating regulatory T cells is closely related to their lower sensitivity to H2O2-induced apoptosis in gastric and esophageal cancer.2013

    • Author(s)
      Izawa S
    • Journal Title

      Cancer Immunol Immunother

      Volume: 62(1) Issue: 1 Pages: 161-70

    • DOI

      10.1007/s00262-012-1327-0

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Liver stiffness measured by magnetic resonance elastography as a risk factor for hepatocellular carcinoma: a preliminary case-control study.2013

    • Author(s)
      Motosugi U
    • Journal Title

      Eur Radiol

      Volume: 23(1) Issue: 1 Pages: 156-62

    • DOI

      10.1007/s00330-012-2571-6

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Lapatinib acts on gastric cancer through both antiproliferative function and augmentation of trastuzumab-mediated antibody-dependent cellular cytotoxicity.2012

    • Author(s)
      Shiraishi K
    • Journal Title

      Gastric Cancer

      Volume: Epub ahead of print Issue: 4 Pages: 571-80

    • DOI

      10.1007/s10120-012-0219-5

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Y.Platelet activation receptor CLEC-2 regulates blood/lymphatic vessel separation by inhibiting proliferation, migration, and tube formation of lymphatic endothelial cells.2012

    • Author(s)
      Osada, M., Inoue, O., Ding, G., Shirai, T., Ichise, H., Hirayama, K., Takano, K., Yatomi, Y., Hirashima, M., Fujii, H., Suzuki-Inoue, K., Ozaki
    • Journal Title

      The Journal of biological chemistry.

      Volume: 287 Issue: 26 Pages: 22241-22252

    • DOI

      10.1074/jbc.m111.329987

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interleukin-17A Plays a Pivotal Role in Polymicrobial Sepsis According to Studies Using IL-17A Knockout Mice.2012

    • Author(s)
      Ogiku M
    • Journal Title

      J Surg Res

      Volume: 174(1) Issue: 1 Pages: 142-9

    • DOI

      10.1016/j.jss.2010.11.901

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Kupffer cell inhibition exacerbates but splenectomy prevents mortality in a rat septic peritonitis model2012

    • Author(s)
      Hiroshi Kono
    • Journal Title

      Journal of Surgical Research

      Volume: 175(1) Issue: 1 Pages: 101-112

    • DOI

      10.1016/j.jss.2011.02.031

    • Related Report
      2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Interleukin-17A Plays a Pivotal Role in Polymicrobial Sepsis According to Studies Using IL-17A Knockout Mice.2012

    • Author(s)
      Masahito Ogiku
    • Journal Title

      J Surg Res

      Volume: 174 Pages: 142-149

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of IL-17A in neutrophil recruitment and hepatic injury after warm ischemia-reperfusion mice.2011

    • Author(s)
      Hiroshi Kono
    • Journal Title

      J Immunol.

      Volume: 187 Pages: 4818-4825

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Glycyrrhizin prevents liver injury by inhibition of high-mobility group box 1 production by Kupffer cells after ischemia-reperfusion in rats.2011

    • Author(s)
      Masahito Ogiku
    • Journal Title

      J Pharmacol Exp Ther

      Volume: 339 Pages: 93-98

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] HCV-related proteins activate Kupffer cells isolated from human liver tissues.2011

    • Author(s)
      Naohiro Hosomura
    • Journal Title

      Dig Dis Sci.

      Volume: 56 Pages: 1057-1064

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of macrophage colony-stimulating factor in polymicrobial sepsis according to studies using osteopetrotic (op/op) mice.2011

    • Author(s)
      Masahito Ogiku
    • Journal Title

      J Surg Res

      Volume: 169 Pages: 106-116

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Liver regeneration is impaired in macrophage colony stimulating factor deficient mice after partial hepatectomy: the role of M-CSF-induced macrophages.2011

    • Author(s)
      Hidetake Amemiya
    • Journal Title

      J Surg Res

      Volume: 165 Pages: 59-67

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Remarks]

    • URL

      http://erdb.yamanashi.ac.jp/rdb/A_Index.Main

    • Related Report
      2013 Final Research Report
  • [Remarks] 山梨大学研究者総覧

    • URL

      http://erdb.yamanashi.ac.jp/rdb/A_DispInfo.List/3_70.html

    • Related Report
      2012 Research-status Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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