Multiple organ failure and macrophage function in severe liver injury: Toll-like receptor and endotoxin clearance

严重肝损伤时的多器官衰竭和巨噬细胞功能:Toll 样受体和内毒素清除

基本信息

  • 批准号:
    15590678
  • 负责人:
  • 金额:
    $ 1.47万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2003
  • 资助国家:
    日本
  • 起止时间:
    2003 至 2005
  • 项目状态:
    已结题

项目摘要

Role of innate immunity in the progression of liver injury was investigated in various experimental models of rats.Firstly, Acute hepatic failure (AHF) was induced in rats by injection of D-galactosamine (GalN, 1g/kg b.w.). In this model, the expression of Toll-like receptor (TLR) 4 mRNA of Kupffer cells was increased compared with controls but those of splenic macrophages and alveolar macrophages did not change. The expressions of liver TNF-α mRNA and TLR4 mRNA were increased in parallel with the progression of liver injury.Secondly, AHF with multiple organ failure was induced in rats by the concomitant administration of GalN (500mg/kg b.w.) and endotoxin (LPS; E.coli 055:B55,50μg/kg b.w.). In this model, more than 90% animals died of AHF within 24 hrs after the injection of GalN and LPS. The expression of liver TNF-α mRNA and CD14 mRNA were increased in parallel with the progression of liver injury. However, TLR4 mRNA was down-regulated at first (at 1lhr and 3hr) and recovered later (at 24hr) in survivors. TLR4 antagonist E5564 revealed rescue effect on this lethal AHF model.Thirdly, the expressions of liver TNF-α mRNA, CD14 mRNA and TLR4 mRNA were gradually increased with the progression of inflammation and fibrosis in non-alcoholic steatohepatitis (NASH) of rat induced by choline-deficient 1-amino acid-defined (CDAA) diet. This suggests that gut-derived endotoxin may activate TLR4-TNF-α axis and induce liver injury in this NASH model.In conclusion, activated innate immunity through TLR4 may be important in the development and progression of AHF and NASH.
本研究采用多种动物实验模型,观察天然免疫在肝损伤中的作用。首先,用D-氨基半乳糖(GalN,1g/kg b.w.)与对照组相比,模型组枯否细胞Toll样受体(TLR)4 mRNA表达明显增加,而脾巨噬细胞和肺泡巨噬细胞TLR 4 mRNA表达无明显变化。(2)用GalN(500 mg/kg b.w.)诱导大鼠急性心力衰竭(AHF)伴多器官功能衰竭(MODS)模型。和内毒素(LPS;大肠杆菌055:B55,50μg/kg b.w.)。在该模型中,超过90%的动物在注射GalN和LPS后24小时内死于AHF。肝组织TNF-α mRNA和CD 14 mRNA的表达随肝损伤程度的加重而增加。而在存活者中,TLR 4 mRNA首先下调(在11小时和3小时),随后恢复(在24小时)。TLR 4拮抗剂E5564对该致死性AHF模型有一定的挽救作用。第三,在胆碱缺乏1-氨基酸限定(CDAA)饮食诱导的非酒精性脂肪性肝炎(NASH)大鼠模型中,随着炎症和纤维化的进展,肝脏TNF-α mRNA、CD 14 mRNA和TLR 4 mRNA的表达逐渐增加。提示肠源性内毒素可能通过激活TLR 4-TNF-α轴而导致NASH肝损伤,提示TLR 4介导的天然免疫激活可能在AHF和NASH的发生发展中起重要作用。

项目成果

期刊论文数量(18)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
【アルコールによる臓器障害と線維化】アルコール性肝障害と多臓器不全におけるエンドトキシン,サイトカインおよびマクロファージの意義
【酒精引起的器官损伤和纤维化】内毒素、细胞因子和巨噬细胞在酒精性肝损伤和多器官衰竭中的意义
  • DOI:
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Koido S;Hara E;Homma S;Torii A;Toyama Y;Kawahara H;Watanabe M;Yanaga K;Fujise K;Tajiri H;Gong J;Toda G.;福井 博
  • 通讯作者:
    福井 博
中谷吉宏, 福井 博, 他: "急性アルコール投与ラットにおける各種マクロファージのTNF-α産生能におよぼすEP4受容体アゴニストの影響"アルコールと医学生物学. 23. 98-104 (2003)
Yoshihiro Nakatani、Hiroshi Fukui 等人:“EP4 受体激动剂对急性酒精给药大鼠中各种巨噬细胞产生 TNF-α 能力的影响”《酒精与医学生物学》23. 98-104 (2003)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Relation of endotoxin, endotoxin binding proteins and macrophages to severe alcoholic liver injury and multiple organ failure
Endotoxin clearance and its relation to hepatic and renal disturbances in rats with liver cirrhosis
  • DOI:
    10.1034/j.1600-0676.2001.210110.x
  • 发表时间:
    2001-02-01
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Nakatani, Y;Fukui, H;Tsujii, T
  • 通讯作者:
    Tsujii, T
The production of tumor necrosis factor-alpha by macrophages in rats with acute alcohol loading
急性酒精负荷大鼠巨噬细胞产生肿瘤坏死因子-α
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FUKUI Hiroshi其他文献

FUKUI Hiroshi的其他文献

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{{ truncateString('FUKUI Hiroshi', 18)}}的其他基金

Single crystal elasticity of iron-bearing bridgmanite under lower-mantle conditions by the inelastic x-ray scattering method
非弹性X射线散射法研究下地幔条件下含铁桥锰矿的单晶弹性
  • 批准号:
    19H02004
  • 财政年份:
    2019
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Determination of elastic wave velocities of iron-bearing magnesium silicate under lower mantle pressure conditions by means of inelastic X-ray scattering
非弹性X射线散射测定低地幔压力条件下含铁硅酸镁的弹性波速
  • 批准号:
    19740327
  • 财政年份:
    2007
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
マクロファージと肝障害:Toll-like受容体制御による新規治療の探索
巨噬细胞和肝损伤:通过Toll样受体调节寻找新的治疗方法
  • 批准号:
    19590784
  • 财政年份:
    2007
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Emndotoxin binding proteins and endotoxin-mediated macrophage reaction : Prospect for future treatment of liver cirrhosis
内毒素结合蛋白和内毒素介导的巨噬细胞反应:肝硬化未来治疗的展望
  • 批准号:
    11670527
  • 财政年份:
    1999
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
BIOORGANIC STUDIES ON BIOFUNCTIONAL COMPONENTS IN VEGETABLES FOR CHEMICAL BREEDING
化学育种蔬菜中生物功能成分的生物有机研究
  • 批准号:
    11660113
  • 财政年份:
    1999
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Macrophage functions in severe liver disturbance and multiple organ failure
巨噬细胞在严重肝功能紊乱和多器官衰竭中的功能
  • 批准号:
    08670612
  • 财政年份:
    1996
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Chemical and biofunctional analysis for chemical breeding of vegetables
蔬菜化学育种的化学和生物功能分析
  • 批准号:
    08660138
  • 财政年份:
    1996
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Endotoxin inactivation by endotoxin binding proteins : Significance in severe liver disturbances
内毒素结合蛋白灭活内毒素:在严重肝脏疾病中的意义
  • 批准号:
    06670578
  • 财政年份:
    1994
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
How does a plant express its secondary metabolism in the special tissues?
植物如何在特殊组织中表达其次生代谢?
  • 批准号:
    05660120
  • 财政年份:
    1993
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Endogenous Inducer of secondary Metabolism in Lithospermum erythrorhizon Cell Cultures
紫草细胞培养物次生代谢的内源诱导剂
  • 批准号:
    03670998
  • 财政年份:
    1991
  • 资助金额:
    $ 1.47万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

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Indoor endotoxin concentrations and the risk of airborne infection and allergy symptoms
室内内毒素浓度与空气传播感染和过敏症状的风险
  • 批准号:
    23H01573
  • 财政年份:
    2023
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    $ 1.47万
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Aiming at a new target in endotoxin-associated lung damage: The Ig domain 3 of ICAM-1
瞄准内毒素相关肺损伤的新靶点:ICAM-1 的 Ig 结构域 3
  • 批准号:
    479050
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    2023
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Out of Time: Biomedicine, Endotoxin Detection, and the Plight of the Horseshoe Crab
过时的:生物医学、内毒素检测和鲎的困境
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    10577633
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    2023
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Development of a novel strategy of circulatory management of septic shock with 2-Methyl-2thiazoline
使用 2-甲基-2噻唑啉开发感染性休克循环管理新策略
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针对内毒素相关肺损伤的新靶点:ICAM-1 的 Ig 结构域 3
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    BB/V50936X/1
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Does endotoxin administration increase alcohol consumption in individuals with AUD?
内毒素给药是否会增加 AUD 患者的饮酒量?
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AlphaBET - Endotoxin detection for the 21st Century
AlphaBET - 21 世纪的内毒素检测
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净水系统中优势产内毒素菌的理化特性及控制措施的阐明
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