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

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591984
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: University 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
• 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

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.

Research Products

• [Journal Article] Typical fibrolamellar hepatocellular carcinoma in a Japanese boy : report of a case (2013)
  • Author(s): Matsuda M, Amemiya H, Kawaida H, Okamoto H, Hosomura N, Asakawa M, Sano K, Motosugi U, Ichikawa T, Nakazawa T, Fujii H.
  • Journal Title: Surg Today
  • DOI: 10.1007/s00595-013-0653-y
  • Peer Reviewed
• [Journal Article] Diagnostic criteria for pancreaticobiliary maljunction 2013 (2013)
  • Author(s): Kamisawa T, Ando H, Hamada Y, Fujii H, Koshinaga T, Urushihara N, Itoi T, Shimada H.
  • Journal Title: J Hepatobiliary Pancreat Sci.
  • DOI: 10.1002/jhbp.57
  • Peer Reviewed
• [Journal Article] Presence of a hypovascular hepatic nodule sh owing hypointensity on hepatocyte-phase image is a risk factor for hyp ervascular hepatocellular carcinoma (2013)
  • Author(s): Ichikawa S, Ichikawa T, Motosugi U, Sano K, Morisaka H, Enomoto N, Mat suda M, Fujii H, Araki T.
  • Journal Title: J Magn Reson Imaging
  • DOI: 10.1002/jmri.24164
  • Peer Reviewed
• [Journal Article] Macrophage colony-stimulating factor plays a pivotal role in chemically induced hepatocellular carcinoma in mice (2013)
  • Author(s): Hara M, Kono H, Furuya S, Hirayama K, Tsuchiya M, Fujii H.
  • Journal Title: He patol Res.
  • DOI: 10.1111/hepr.12174
  • Peer Reviewed
• [Journal Article] Extrahepatic bile duct measurement by using transa bdominal ultrasound in Japanese adults : multi-center prospective study (2013)
  • Author(s): Itoi T, Kamisawa T, Fujii H, Inui K, Maguchi H, Hamada Y, Nakano T, And o H, Koshinaga T, Shibagaki K, Obayashi T, Miyazawa Y.
  • Journal Title: J Gastroenterol Volume: 48(9) Pages: 1045-50
  • DOI: 10.1007/s00535-012-0702-0
  • Peer Reviewed
• [Journal Article] The MAPK Pathway Is a Predominant Regulator of HLA-A Expression in Es ophageal and Gastric Cancer (2013)
  • Author(s): Mimura K, Shiraishi K, Mueller A, I zawa S, Kua LF, So J, Yong WP, Fuji i H, Seliger B, Kiessling R, Kono K.
  • Journal Title: J Immunol Volume: 191(12) Pages: 6261-72
  • DOI: 10.4049/jimmunol.1301597
  • Peer Reviewed
• [Journal Article] Cervical lymph node d issection for clinically submucosal carcinoma of the thoracic esophagu ss (2013)
  • Author(s): Kosugi S, Kawaguchi Y, Kanda T, Ish ikawa T, Sakamoto K, Akaike H, Fuji i H, Wakai T.
  • Journal Title: Ann Surg Oncol Volume: 20(12) Pages: 4016-21
  • DOI: 10.1245/s10434-013-3141-0
  • Peer Reviewed
• [Journal Article] Bayesian prediction for liver fibrosis staging : combined use of elastography and serum fibrosis markers (2013)
  • Author(s): Motosugi U, Ichikawa T, Araki T, Matsuda M, Fujii H, Enomoto N.
  • Journal Title: Hepatology Volume: 58(1) Pages: 450-1
  • DOI: 10.1002/hep.26144
  • Peer Reviewed
• [Journal Article] Pancreatobiliary reflux in individuals with a normal pancreaticobiliary junction : a prospective multicenter study. The committee of Diagnostic Criteria of The Japanese Study Group on Pancreaticobiliary Maljunction (2013)
  • Author(s): Horaguchi J, Fujita N, Kamisawa T, Honda G, Chijiiwa K, Maguchi H, Tan aka M, Shimada M, Igarashi Y, Inui K, Hanada K, Itoi T, Hamada Y, Kosh inaga T, Fujii H, Urushihara N, And o H.
  • Journal Title: J Gastroenterol
  • DOI: 10.1007/s00535-013-0837-7
  • Peer Reviewed
• [Journal Article] Early hepatocellular carci nomas showing isointensity or hyper intensity in gadoxetic acid-enhanced, hepatocyte-phase magnetic resonance images (2013)
  • Author(s): Chen N, Motosugi U, Sano K, Ichikawa T, Nakano M, Morisaka H, Ichikawa S, Matsuda M, Fujii H, Enomoto N, Araki T.
  • Journal Title: J Comput Assist Tomogr Volume: 37(3) Pages: 466-9
  • DOI: 10.1097/RCT.0b013e3182873799
  • Peer Reviewed
• [Journal Article] Real-time diagnosis of chemically induced hepatocellular car cinoma using a novel mass spectrome try-based technique (2013)
  • Author(s): Yoshimura K, Mandal MK, Hara M, Fuj ii H, Chen LC, Tanabe K, Hiraoka K, Takeda S.
  • Journal Title: Anal Biochem Volume: 4 41(1) Pages: 32-7
  • DOI: 10.1016/j.ab.2013.06.017
  • Peer Reviewed
• [Journal Article] Small-cell carcinoma of the breast with squamou s differentiation (2013)
  • Author(s): Kawasaki T, Bussolati G, Castellano I, Marchiò C, Daniele L, Molinaro L, Kondo T, Katoh R, Inoue S, Fujii H, Sugai T, Sapino A.
  • Journal Title: Histopathology Volume: 63(5) Pages: 739-741
  • DOI: 10.1111/his.12201
  • Peer Reviewed
• [Journal Article] Interleukin-17A plays a pivotal role after partial hepatectomy in mice (2013)
  • Author(s): Furuya S, Kono H, Hara M, Hirayama K, Tsuchiya M, Fujii H.
  • Journal Title: J Surg Res. Volume: 184(2) Pages: 838-46
  • DOI: 10.1016/j.jss.2013.03.033
  • Peer Reviewed
• [Journal Article] Interleukin-17A plays a pivotal role in cholest aticliver fibrosis in mice (2013)
  • Author(s): Hara M, Kono H, Furuya S, Hirayama K, Tsuchiya M, Fujii H.
  • Journal Title: J Surg Res. Volume: 183(2) Pages: 574-82
  • DOI: 10.1016/j.jss.2013.03.025
  • Peer Reviewed
• [Journal Article] Lapatinib acts on gastric cancer through both antiproliferative function and augmentation of trastuzumab-mediated antibody-dependent cellular cytotoxicity (2013)
  • Author(s): Shiraishi K, Mimura K, Izawa S, Inoue A, Shiba S, Maruyama T, Watanabe M, Kawaguchi Y, Inoue M, Fujii H, Kono K.
  • Journal Title: Gastric Cancer Volume: 16(4) Pages: 571-580
  • DOI: 10.1007/s10120-012-0219-5
  • Peer Reviewed
• [Journal Article] Increased prevalence of tumor-in filtrating regulatory T cells is closely related to their lower sensitivity to H2O2-induced apoptosis in gastric and esophageal cancer (2013)
  • Author(s): Izawa S, Mimura K, Watanabe M, Maruyama T, Kawaguchi Y, Fujii H, Kono K.
  • Journal Title: Cancer Immunol Immunother Volume: 62(1) Pages: 161-70
  • DOI: 10.1007/s00262-012-1327-0
  • 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, Ichikawa T, Koshiishi T, Sano K, Morisaka H, Ichikawa S, Enomoto N, Matsuda M, Fujii H, Araki T.
  • Journal Title: Eur Radiol Volume: 23(1) Pages: 156-62
  • DOI: 10.1007/s00330-012-2571-6
  • Peer Reviewed
• [Remarks]
  • URL: http://erdb.yamanashi.ac.jp/rdb/A_Index.Main