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Study on the regulation mechanism by endogenous bioactive substances produced by hepato-sinusoidal cells.

Research Project

Project/Area Number 03670372
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionOsaka City University

Principal Investigator

KUROKI Tetsuo (1992)  Osaka City University, School of Medicine, Lecturer, 医学部, 講師 (30047328)

溝口 靖紘 (1991)  大阪市立大学, 医学部, 助教授 (00094491)

Co-Investigator(Kenkyū-buntansha) NAKAJIMA Shinya  Osaka City University, School of Medicine, Research Associate, 医学部, 助手 (50180287)
SHIOMI Susumu  Osaka City University, School of Medicine, Lecturer, 医学部, 講師 (30170848)
SEKI Shuichi  Osaka City University, School of Medicine, Lecturer, 医学部, 講師 (50145778)
岡 博子  大阪市立大学, 医学部, 助手 (40169090)
黒木 哲夫  大阪市立大学, 医学部, 講師 (30047328)
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1991: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsHepato-sinusoidal cells / Kupffer cells / Sinusoidal-endothelial cells / Cytokine cascade / Arachidic acids cascade / Liver infiltrated macrophages / prostaglandins / Interleukins / アラキドン酸カスケード / Ca^<2+> / プロスタグランジン / サイトカインカスケ-ド / アラキドン酸カスケ-ド / 肝浸潤マクロファ-ジ / ブロスタグランジン / インタ-ロイキン
Research Abstract

Hepatic sinusoidal cells are mainly constituted by Kupffer cells, hepatic sinusoidal endothelial cells, Ito cells and pit cells. In this study, we focused Kupffer cells and hepatic sinusoidal endothelial cells to analyze the role of endogenous activating substances on the regulation network in the liver.
1) The production of arachidic acid metabolites and lipid metabolites by hepatic sinusoidal cells. Once rat Kupffer cells were stimulated by biological response modifiers such as lipopolysaccharide (LPS), heat-killed Propionibacterium acnes (P. acnes) and OK-432, they produced and secreted prostaglandin (PG) E2, 6-keto PGF1alpha and thromboxane (TX)B2. However, they produced PGD2 in rest state. This change was due to the induction of cyclo-oxygenase that is located on the upstream of the PG metabolic pathway. The stimulated Kupffer cells did not produce such PG metabolites unless they were inculated without Ca^<2+>, or with Ca^<2+>-chylates or calmodulin inhibitors, suggesting that their production by stimulated Kupffer cells might depend on intracellular and extracellular Ca as well as calmodulin. When Kupffer cells and hepatic sinusoidal endothelial cells were incubated with Ca ionophore, they produced platelet activating factor (PAF), a biological active lipid metabolite.
2) Cytokines produced by hepatic sinusoidal cells. LPS-stimulated Kupffer cells produced interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-alpha. This was also obsereved by stimulated hepatic sinusoidal endothelial cells. Interferon-gamma, a macrophage activating factor, led Kupffer cells to produce these cytokines, while PGE1 or PGI2 reduced such cytokine production. These results suggested the existence of the inter-and intra-regulation systems among cytokine network and arachidic acid metabolite cascade in the hepatic sinusoidal cells.

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] Mizoguchi,Y.,et al.: "Effect of Gomisin A in an immanologically-induced acule hepatic faihue model" Planta Medica. 57. 11-14 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Mizoguchi,Y.,et al.: "Effects of irsoglandine maleate in an experimentally induced acute hepatic failure model using mice." Gostroenterologica Jpn.26. 177-181 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Mizoguchi,Y.,et al.: "Effect of Gomisin A in the prevention of acute hepatic failure induction" Planta Medica. 57. 320-324 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Mizoguchi,Y.,et al.: "Effects of arachidonic acid metabolites and interleukin 1 on platelet activating factor production by hepatic sinusoidal endothelial cells from mice." J.Gastroenterology Hepatology. 6. 283-288 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kawada,N.,et al: "Interferon 8 modulates production of interleulcin 1 and tumor necrosis factor by murine keepffer cells." Liver. 11. 42-47 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Mizoguchi,Y.,et al: "The effect of lipo prostaglandin E_1 on the production of interleukin1 and PAF by hepatie sinusoidal endothelial cells in mice." Osaka City Medical Journal. 37. 69-78 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kawada,N.,et al: "Possible induction of fatty acid cyclo-oxygenase in lipopolysaccharide-stimulated rat kupffer cells." Gastroenterology. 103. 1026-1033 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kawada,N.,et al: "Calcium-dependent prostaglandin biosynthesis by lipopolysaccharide-stimulated rat kupffer cells." Prostaglandins Leukotrienes and Essential Fatty Acids. 47. 209-214 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kawada,N.,et al: "Enhancement of prostaglandin E_2 production by liver macrophages(Keepffer cells)after stimulation with biological response modifiers." Prostaglandins Leukofrienes and Essevtial Fatly Acids. 46. 105-110 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kawada,N.,et al: "Increased 5-lipoxygenase activity in massive hepatic cell necrosis in the rat correlates with neutrophil infiltration" Hepatology. 16. 462-468 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tsutsui,H.,et al: "Importance of direct hepatocytolysis by liver macrophages in experimental fulminant hepatitis." Hepato-Gastroenterology. 39. 553-559 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Mizoguchi,Y.,et al: "Network of cytokine and arachidonic acicl cascade in acute hepatic failure" Gastroenterologica Japonica. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 溝口 靖紘: "肝とアルコール・肝再生・肝細胞障害" 中外医学社, 13 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 溝口 靖紘: "最新医学からのアプローチ・サイトカイン・病態解明と診断・治療への応用" メジカルビュー社,

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kawada,N.,et al: "Frontiers of Mucosal Immunology vol.2" Excerpta Medica, 4 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tsutsui,H.,et al: "Frontiers of Mucosal Immunology vol.2" Excerpta Medica, 4 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Mizoguchi Y., et al.: "Effect of Gomisin A in an immunologically-induced acute hepatic failure model." Planta Medica. 57. 11-14 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Mizoguchi Y., et al.: "Effects of irsoglandine maleate in an experimentally-induced acute hepatic failure model using mice." Gastroenterologia Jpn. 26. 177-181 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Mizoguchi Y., et al.: "Effect of Gomisin A in the prevention of acute hepatic failure induction." Planta Medica. 57. 320-324 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Mizoguchi Y., et al.: "Effects of arachidic acid metabolites and interleukin 1 on platelet activating factor production by hepatic sinusoidal endothelial cells from mice." J. Gastroenterology Hepatology. 6. 283-288 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kawada N., et al.: "Interferon g modulates production of interleukin 1 and tumor necrosis factor by murine Kupffer cells." Liver. 11. 42-47 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Mizoguchi Y., et al.: "The effect of lipoprostaglandin E1 on the production of interleukin 1 and PAF by hepatic sinusoidal endothelial cells in mice." Osaka City Medical Journal. 37. 69-78 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kawada N., et al.: "Enhance ment of prostaglandin E2 production by liver macrophages (Kupffer cells) stimulated with biological response modifiers." Prostaglandins Leukotrienes Essential Fatty Acids. 46. 105-109 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kawada N., et al.: "Regulation of cytokines and arachidic acid cascade by Kupffer cells and hepatic sinusoidal endothelial cells." In Frontiers of mucosal immunology. (Elsevier Science Publishers B.V.). vol.2. 197-200 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tsutsui H., et al.: "Studies on experimentally-induced acute hepatic failure : Possible involvement of hepatocytotoxic factor produced by liver adherent cells." In Frontiers of mucosal immunology. (Elsevier Science Publishers B.V.). vol.2. 377-380 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kawada N., et al.: "Increased 5-lipoxygenase activity in massive ehpatic cell necrosis in the rat correlate with neutrophile infiltration." Hepatology. 16. 462-468 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kawada N., et al.: "Possible induction of fatty acid cyclo-oxygenase in lipopolysaccharide stimulated rat Kupffer cells." Gastroenterology. 103. 1026-1033 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kawada N., et al.: "Calcium-dependent prostaglandin biosynthesis by lipopolysaccharide-stimulated rat Kupffer cell." Prostaglandins Leukotrienes Essential Fatty Acids. 47. 209-214 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tsutsui H., et al.: "Importance of direct hepatocytolysis by liver macrophages in experimental fulminant hepatitis." Hepato-Gastroenterol.39. 553-559 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Mizoguchi Y., et al.: "Network of cytokine and arachidic acid cascade in acute hepatic failure." Gastroenterologica Jpn.(1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kawada N., et al.: Excerpta Medica Frontiers of Mucosal Immunology. vol.2. 4 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Tsutsui H., et al.: Excerpta Medica Frontiers of Mucosal Immunology. vol.2. 4 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kawada,N.,et al: "Possible induction of fatty acid cyclo-oxygenase in lipopolysaccharide-stimulated rat Kupffer cells." Gastroenterology. 103. 1026-1033 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kawada,N.,et al: "Calcium-dependent prostaglandin biosynthesrs by lipopolysaccharide-stimulated rat Kupffer cells." Prostaglandins Leukotrienes and Essential Fatty Acids. 47. 209-214 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kawada,N.,et al: "Enhancement of prostaglandin E2production by liven macrophages(Kepffer cells)after stimulation with biological response modifiers." Prostaglandins Leukotrienes and Essential Fatly Acids. 46. 105-110 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kawad,N.,et al: "Increased 5-lipoxygenase activity in massive hepatic cell necrosis in the rat correlates with neupophil infiltration." Hepatology. 16. 462-468 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tsutsui,H.,et al: "Importance of direct hepatocytolysis by liver macrophages in experimental fulminant hepatitis." Hepato-Gastronenterology. 39. 553-559 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mizoguchi,Y.,et al: "Network of cytokine and arachidonic acid cassade in acute hepatic failure" Gastroenterologica Japonica. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kawada,N,et al: "Frontiers of Mucosal Immunology vol.2" Excerpta Medica, 4 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tsutsui,H,et al: "Frontiers of Mucosal Immunology vol.2" Excerpta Medica, 4 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Mizoguchi Y: "Effect of Gomisin A in an immunologicallyーinduced acute hepatic failure model." Planta Med. 57. 11-14 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Mizoguchi Y: "Effect of irsoglandine maleate in an experimentallyーinduced acute hepatic failure model using mice." Gastroenterologica Jpn. 26. 177-181 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Mizoguchi Y: "Effect of Gomisin A in the prevention of acute hepatic failure induction." Planta Med. 57. 320-324 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Mizoguchi Y.: "Effects of arachidonic acid metabolites and interleukin 1 on platelet activating factor production by hepatic sinusoidal endothelial cells from mice." J Gostroenterology Hepatology. 6. 283-288 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kawada N.: "Interferon γ modulates production of interleukin 1 and tumor necrosis factor by murine Kupffer cells." Liver. 11. 42-47 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Mizoguchi Y.: "The Effect of lipo prostaglandin E_1 on the production of interleukin 1 and PAF by hepatic sinusoidal endothelial cells in mice." Osaka City Med J. 37. 69-78 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 溝口 靖紘: "肝とアルコ-ル・肝再生・肝細胞障害" 中外医学社, 13 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 溝口 靖紘: "最新医学からのアプロ-チ、サイトカイン、病態解明と診断・治療への応用" メジカルビュ-社, 10 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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