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Emndotoxin binding proteins and endotoxin-mediated macrophage reaction : Prospect for future treatment of liver cirrhosis

Research Project

Project/Area Number 11670527
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionNara Medical University

Principal Investigator

FUKUI Hiroshi  Nara Medical University, 3rd Dept of Internal Medicine, Professor, 医学部, 教授 (80145838)

Co-Investigator(Kenkyū-buntansha) KURIYAMA Shigeki  Kagawa Medical University, 3rd Dept of Internal Medicine, Professor, 医学部, 教授 (50244710)
UEMURA Masahito  Nara Medical University, 3rd Dept of Internal Medicine, Lecturer, 医学部, 講師 (90151836)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordsendotoxin / endotoxin-binding protein / liver cirrhosis / tumor necrosis factor-α / macrophage / Kupffer cell / アルコール
Research Abstract

1.In order to attain more physiological condition in the evaluation of macrophage function, we added 1% rat serum as a source of lipopolysaccharide (LPS) binding protein (LBP) and analyzed LPS-stimulated TNF-α production by various rat macrophages. TNF-α production of alveolar macrophages was much greater than Kupffer cells.
2.Cytokine production of various macrophages was evaluated in rat with liver cirrhosis. TNF-α and IL1-β production by Kupffer cells was low and those by alveolar macrophages was high in cirrhotic rats compared with controls. Hepatocellular carcinoma grew more rapidly in cirrhotic liver, which may be partly related to depressed TNF-α and IL1-β production by Kupffer cells.
3.Prostaglandin EP-4 agonist suppressed TNE-α production of rat -Kupffer cells and splenic macrophages. An addition of EP-4 agonist tended to antagonize the inhibitory effect of LPS on albumin synthesis of rat hepatocytes in the co-culture system.
These results suggest that the modulation of macrophage function may become future therapeutic approach to liver cirrhosis.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Tshujimoto T, Fukui et al.: "Augmented hepatocellular carcinoma progression and depressed Kupffer cell activity in rat cirrhotic livers"Int J Oncol. 18. 41-47 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakatani Y, Fukui et al.: "Endotoxin clearance and its relation to hepatic and renal disturbances in rats with liver cirrhosis"Liver. 21. 64-70 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakatani Y, Fukui et al.: "Effect of alcohol on the secretion of tumor necrosis factor-alpha by macrophages in the presence of rat serum"Alcohol Clin Exp Res. 26. 81S-85S (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H Fukui, T Tsujita, M Matsumoto, et al.: "Endotoxemia in chronic hepatitis and cirrhosis : epiphenomenon or of pathological relevance?"Falk Symposium 100 Gut and Liver (eds by HE Blum, Ch Bode, J Ch Bode, et al.) (Kluwer Academic Publishers, Dordrecht, Boston, London). 251-262 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujimoto M, Uemura M, Nakatani Y, Tsujita S, Hopo K, Tamagawa T, Kitano H, Kikukawa M, Ann, T, Ishii, Y, Kojima H, Sakurai S, Tanaka R, Namisaki T, Noguchi R, Higashino T, Kikuchi E, Nishimura K, takaya A, Fukui H: "Plasma endotoxin and serum cytokine levels in patients with alcoholic hepatitis : relation to severity of liver disturbance"Alcohol Clin Exp Res. 24. 48S-54S (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsujimoto T, Kuriyama S, Yamazaki M, Nakatani Y, Okuda H, Yoshiji H, Fukui H: "Augmented hepatocellular carcinoma progression and depressed Kupffer cell activity in rat cirrhotic livers"Int J Oncol. 18. 41-47 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakatani Y, Fukui H, Kitano H, Nagamoto I, Tsujimoto T, Kuriyama S, Kikuchi E, Hoppou K, Tsujii T: "Endotoxin clearance and its relation to hepatic and renal disturbances in rats with liver cirrhosis"Liver. 21. 64-0 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nakatani Y, Fukui H, Kitazawa T, Fujimoto M, Yamao J, Uemura M: "Effect of alcohol on the secretion of tumor necrosis factor-alpha by macrophages in the presence of rat serum"Alcohol Clin Exp Res. 26. 81S-85S (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Uemura M, Fukui Hetal: "Enhanced urinary excretion of cysteinyl leukotrienes in patients with acute alcohol intoxication"Gastroenterology. 118(6). 1140-1148 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujimoto M, Fukui H et al.: "Prognostic factors in severe alcoholic liver injury"Alcohol Clin Exp Res. 23(Suppl.4). 33S-38S (1999)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kojima H, Fukai H et al.: "Endothelin-1 plays a major role in portal hypertension of hiliary cirrhotic rats through endothelin receptor subtype B together with subtype A in vivo"J Hepatol. 34(6). 805-811 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujimoto M,Fukui H et al: "Plasma endotoxin and serum cytokine levels in patients with alcoholic hepatitis : relation to severity of liver disease"Alcohol Clin Exp Res. 24(Suppl 4). 48S-54S (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakatani Y,Fukui H et al: "Endotoxin clearance and its relation to hepatic and renal disturbances in rats with liver cirrhosis"Liver. 21・1. 64-70 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsujimoto T.Fukui H et al: "Augmented hepatocellular carcinoma progression and depressed Kupffer cell activity in rat cirrhotic livers"Int J Oncol. 18・1. 41-47 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fukui H,Tsujita T,et al: "Endotoxemia in chronic hepatitis and cirrhosis.Epiphenomenum or of pathological relevance?"Gut and the Liver (Falk Symposium 100). 251-262 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] 北野浩行,福井 博 他: "アルコール投与ラットのエンドトキシン処理機構"アルコールと医学生物学. 17. 180-184 (1997)

    • Related Report
      1999 Annual Research Report
  • [Publications] 北野浩行,福井 博 他: "アルコール性肝障害-ラットモデル-"エンドトキシン研究. 1. 67-74 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 福井 博: "エンドトキシン中和物質"集中治療. 11・2. 127-134 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukui H,Uemura M.et al: "Pathophysiology and treatment of cirrhotic ascites"Liver Cirrhosis update. 63-76 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 福井 博,北野浩行 他: "アルコール性肝障害とエンドトキシン:サイトカインとの関連において"箱根シンポジウム. 8. 13-22 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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