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

• Project/Area Number: 20591516
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: University of Yamanashi
• Principal Investigator: FUJII Hideki University of Yamanashi, 大学院・医学工学総合研究部, 教授 (30181316)
• Co-Investigator(Kenkyū-buntansha): KONO Hiroshi 山梨大学, 大学院・医学工学総合研究部, 助教 (40322127)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 人工肝臓補助システム / 肝実質細胞 / 肝kupffer細胞 / サイトカイン / 盲腸結紮穿刺モデル / 肝免疫 / 十全大補湯 / 中鎖脂肪酸 / 人工肝臓システム / Kupffer細胞 / 急性肝不全 / 感染免疫 / op/op mouse / IL-17A KO mouse / 制御性T細胞 / CLPモデル / 肝Kuffer細胞 / スフェロイド / ポリウレタン膜 / 感染制御 / 免疫機能改善 / 肝Kupffer細胞 / 腹腔内感染 / 急性肺障害 / IL-10 / 盲腸結紮穿刺 / 塩化ガドリニウム

Research Abstract

For making up a hybrid type artificial liver support system, functions of the Kupffer cell must be analyzed. As results, the Kupffer cell controlled systemic inflammation such as a sepsis with cytokine network and systemic immune system. And more inflammatory cytokine from the Kupffer cell cause a hepatocellular carcinoma. Activation of the Kupffer cell can be suppressed by administration of some drugs and foods such as medium-chain triglycerides.

Research Products

• [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): Amemiya H, Kono H, Fujii H
  • Journal Title: J Surg Res. 165(1) Pages: 59-67
  • Peer Reviewed
• [Journal Article] HCV-related proteins activate Kupffer cells isolated from human liver tissues (2011)
  • Author(s): Hosomura N, Kono H, Tsuchiya M, Ishii K, Ogiku M, Matsuda M, Fujii H
  • Journal Title: Dig Dis Sci. 56(4) Pages: 1057-1064
  • Peer Reviewed
• [Journal Article] Enteral diets enriched with medium-chain triglycerides and N-3 fatty acids prevent chemically induced experimental colitis in rats. (2010)
  • Author(s): Kono H, Fujii H, Ogiku M, Tsuchiya M, Ishii K, Hara M
  • Journal Title: Transl Res. 156(5) Pages: 282-291
  • Peer Reviewed
• [Journal Article] Gene expression in nontumoral liver tissue and recurrence-free survival in hepatitis C virus-positive hepatocellular car cinoma. (2010)
  • Author(s): Tsuchiya M, Parker JS, Kono H, Matsuda M, Fujii H, Rusyn I
  • Journal Title: Mol Cancer. 9 Pages: 74-74
  • Peer Reviewed
• [Journal Article] Dietary medium-chain trigly cerides prevent chemically induced experimental colitis in rats (2010)
  • Author(s): Kono H, Fujii H, Ishii K, Hosomura N, Ogiku M
  • Journal Title: Transl Res. 155(3) Pages: 131-141
  • Peer Reviewed
• [Journal Article] Interleukin-17A Plays a Pivotal Role in Polymicrobial Sepsis. According to Studies Using IL-17A Knockout Mice. (2010)
  • Author(s): Masahito Ogiku
  • Journal Title: J Surg Res. [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] Enteral diets enriched with medium-chain triglycerides and N-3 fatty acids prevent chemically induced experimental colitis in rats. (2010)
  • Author(s): Hiroshi Kono
  • Journal Title: Translational Research Volume: 156 Pages: 282-291
  • Peer Reviewed
• [Journal Article] Gene expression in nontumoral liver tissue and recurrence-free survival in hepatitis C virus-positive henatocellular carcinoma. (2010)
  • Author(s): Masato Tsuchiya
  • Journal Title: Mol Cancer. Volume: 9 Pages: 74-74
  • Peer Reviewed
• [Journal Article] Dietary olive oil prevents carbon tetrachloride-induced hepatic fibrosis in mice. (2009)
  • Author(s): Tanaka N, Kono H, Ishii K, Hosomura N, Fujii H
  • Journal Title: J Gastroenterol. 44(9) Pages: 983-990
  • NAID: 10025581512
  • Peer Reviewed
• [Journal Article] Medium-chain triglycerides enhance mucous secretion and cell proliferation in the rat. (2009)
  • Author(s): Ishii K, Kono H, Hosomura N, Tsuchiy a M, Ohgiku M, Tanaka N, Fujii H
  • Journal Title: J Gastroenterol. 44(3) Pages: 204-211
  • NAID: 10025173765
  • Peer Reviewed
• [Journal Article] Role of Macrophage Colony-Stimulating Factor in Polymicrobial Sepsis According to Studies Using Osteopetrotic (op/op) Mice. (2009)
  • Author(s): Masahito Ogiku
  • Journal Title: J Surg Res.
  • 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. (2009)
  • Author(s): Hidetake Amemiya
  • Journal Title: J Surg Res.
  • Peer Reviewed
• [Journal Article] Dietary olive oil prevents carbon tetrachloride-induced hepatic fibrosis in mice. (2009)
  • Author(s): Nobuyuki Tanaka
  • Journal Title: J Gastroenterol 44 Pages: 983-990
  • Peer Reviewed
• [Journal Article] Inhibition of the Kupffer cell increases serum high mobility group box 1levels in a rat septic peritonitis model (2009)
  • Author(s): Hiroshi Kono
  • Journal Title: Journal of Surgical Research (In press)
  • Peer Reviewed
• [Journal Article] Protective effect of Juzen Taiho to on hepatocarcinogenesis is mediated through the inhibition of Kupffer cell-induced oxidative stress. (2008)
  • Author(s): Tsuchiya M, Kono H, Matsuda M, Fujii H, Rusyn I
  • Journal Title: Int J Cancer. 123(11) Pages: 2503-2511
  • Peer Reviewed
• [Journal Article] Inhibition of the Kupffer cell and neutralization of IL-10 increase the expression of chemokines in the lung in a rat peritonitis model. (2008)
  • Author(s): Kono H, Fujii H, Tsuchiya M, Hirai Y, Ishii K, Hosomura N, Tanaka N
  • Journal Title: J Surg Res. 150(2) Pages: 169-182
  • Peer Reviewed
• [Journal Article] Inhibition of the Kupffer cell and neutralization of IL-10 increase the expression of chemokines in the lung in a rat peritonitis model (2008)
  • Author(s): Hiroshi Kono
  • Journal Title: Journal of Surgical Research 150 Pages: 169-182
  • Peer Reviewed
• [Journal Article] Protective effect of Juzen-taiho-to on hepatocarciogenesis is mediated through the inhibition of Kupffer cell-induced oxidative stress (2008)
  • Author(s): Masato Tsuchiya
  • Journal Title: Int J Cancer 123 Pages: 2403-2511
  • Peer Reviewed
• [Journal Article] The Kupffer Cell Inhibition Exacerbates but Splenectomy Prevents Mortality in a Rat Septic Peritonitis Model.
  • Author(s): Kono H, Fujii H, Ogiku M, Hara M, Tsuchiya M, Ishii K, Hosomura N
  • Journal Title: J Surg Res. 2011 [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] Interleukin-17A Plays a Pivotal Role in Polymicrobial Sepsis According to Studies Using IL-17A Knockout Mice.
  • Author(s): Ogiku M, Kono H, Hara M, Tsuchiya M, Fujii H
  • Journal Title: J Surg Res.2010 [Epub ahead of print]
  • Peer Reviewed
• [Presentation] Cholestasis-induced hepatic injury and fibrosis are attenuated in IL-17A-deficietnmice. (2010)
  • Author(s): Kono H, Fujii H.
  • Organizer: The Liver Meeting 2010 AASLD's 61st Annual Meeting
  • Place of Presentation: Boston, MA
• [Presentation] Inhibition of the Kupffer cell deteriorates and splenectomy prevents mortality in a rat septic peritonitis model. (2009)
  • Author(s): Kono H, Fujii H, Ogiku M, Ishii K, Hosomura N.
  • Organizer: 60th Annual Meeting of the American Association for the Study of Liver Disease
  • Place of Presentation: Boston, MA
• [Presentation] Specific role of the interleukin-17 in neutrophil recruitment into the liver after ischemia/reperfusion. (2009)
  • Author(s): Kono H, Ogiku M, Hosomura N, Fujii H.
  • Organizer: 60th Annual Meeting of the American Association for the Study of Liver Disease
  • Place of Presentation: Boston, MA
• [Presentation] 細菌性腹膜炎において、肝類洞免疫能の低下はHigh-mobility group protein (HMGB)1発現を増加させる (2008)
  • Author(s): 河野寛
  • Organizer: 第44回日本肝臓学会総会
  • Place of Presentation: 愛媛県県民文化会館
  • Year and Date: 2008-06-05
• [Presentation] 細菌性腹膜炎において、肝類洞免疫能の低下はHigh-mobility group protein (HMGB)1発現を増加させる (2008)
  • Author(s): 河野寛
  • Organizer: 第108回日本外科学会定期学術集会
  • Place of Presentation: 長崎ブリックホール
  • Year and Date: 2008-05-15
• [Remarks]
  • URL: http://sangaku.yamanashi.ac.jp/SearchResearcher/contents/1BB3DE3CA4D2F1C8.html