The effect of intermedilysin on human bile duct cells

intermedilysin对人胆管细胞的影响

基本信息

  • 批准号:
    18592003
  • 负责人:
  • 金额:
    $ 2.4万
  • 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:
    2006
  • 资助国家:
    日本
  • 起止时间:
    2006 至 2007
  • 项目状态:
    已结题

项目摘要

Streptococcus intermedius is a commensal member of the human oral, gastrointestinal and urinary floras, but may also be associated with deep-seated purulent infections, particularly in the liver abscess.It was recently reported that the function of bacterial pore-forming toxins is biphasic. Not only do they act cytolytically on nucleated target cells when present in higher concentrations, but they can also affect signal-transduction pathways in cells when the toxin is present in low, sublytic concentrations. Intermedilysin (ILY), a human-specific pore-forming cytolysin, has been suggested as a potentially important virulence factor of S.intermedius.Whereas Ca^<2+> is a key regulator of cell survival, the breakdown of Ca^<2+> homeostasis due to its sustained elevation was able to trigger cell death. The goals here were to examine whether a low, sublytic concentration of ILY affects Ca^<2+> homeostasis in human bile duct cells by induction of [Ca^<2+>]I oscillation and [Ca^<2+>]I related … More other cell responses (the activation of calcineurin/NFAT pathway, PI3/AKT/MTOR pathway, and endoplasmic reticulum stress).Fron the calcium imaging, five rain ILY treatment generated an increase in[Ca^<2+>]i level from the average base line of 50 nM up to the average peak of 400 nM marked by two repeated oscillations every minute. Increased [Ca^<2+>]i was initially detected in the nuclei of ILY-treated cells subsequently followed with markedly increase in ER area. Immunocytochemistry and Westernbloting analysis, ILY treatment caused activation of calcineurin/NFAT1 signalling pathway and increased expression of AKT(p-S473),BiP, and PTEN. Interestingly the expression of BiP and AKT(p-S473)decreased in an hour post ILY treatment. Calcineurin inhibitor cyclosporine A prevented ILY-induced calcineurin/NFAT1 activation, cell death, and calcium oscillations.ILY in concentration of 10-40 ng/ml capable of inducing calcium oscillations, activation of calcineurin/NFAT1 signalling pathway ; inactivation of PI3K/AKT/MTOR pathway, and caused ER stress disorder resulted non-apoptotic cell death in HuCCT1 cells. Less
中间链球菌是人类口腔、胃肠道和泌尿菌群的共栖成员,但也可能与深层化脓性感染有关,特别是在肝脓肿中。最近有报道称,细菌成孔毒素的功能是双相的。当毒素浓度较高时,它们不仅对有核靶细胞起细胞溶解作用,而且当毒素浓度较低时,它们也可以影响细胞中的信号转导途径。中间溶素(Intermedilysin, ILY)是一种人类特有的成孔细胞溶素,被认为是中间葡萄球菌潜在的重要毒力因子,而Ca^<2+>是细胞存活的关键调节因子,由于Ca^<2+>持续升高而导致细胞内稳态的破坏能够引发细胞死亡。本研究的目的是研究低亚溶浓度的ILY是否通过诱导[Ca^<2+>]I振荡和[Ca^<2+>]I相关的影响人胆管细胞Ca^<2+>稳态。更多其他细胞反应(钙调磷酸酶/NFAT通路、PI3/AKT/MTOR通路和内质网应激的激活)。从钙成像来看,5次降雨ILY处理使[Ca^<2+>]i水平从50 nM的平均基线上升到400 nM的平均峰值,每分钟出现两次重复振荡。在ily处理的细胞中,最初在细胞核中检测到[Ca^<2+>]i升高,随后ER面积明显增加。免疫细胞化学和western blotting分析显示,ILY处理可激活钙调磷酸酶/NFAT1信号通路,增加AKT(p-S473)、BiP和PTEN的表达。有趣的是,在ILY治疗后1小时,BiP和AKT(p-S473)的表达下降。钙调磷酸酶抑制剂环孢素A可阻止ili诱导的钙调磷酸酶/NFAT1活化、细胞死亡和钙振荡。ILY在浓度为10-40 ng/ml时能够诱导钙振荡,激活钙调磷酸酶/NFAT1信号通路;PI3K/AKT/MTOR通路失活,引起内质网应激障碍,导致HuCCT1细胞非凋亡性细胞死亡。少

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Histone-like DNA binding protein of Streptococcus intermedius induces the expression of pro-inflammatory cytokines in human monocytes via activation of ERK1/2 and JNK pathways
  • DOI:
    10.1111/j.1462-5822.2007.01040.x
  • 发表时间:
    2008-01-01
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Liu, Dali;Yumoto, Hiromichi;Miyake, Yoichiro
  • 通讯作者:
    Miyake, Yoichiro
Intermedilysinによる培養ヒト胆管上皮細胞核膜抗原の異所性表出
中间素异位表达培养的人胆管上皮细胞核膜抗原
  • DOI:
  • 发表时间:
    2007
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Liu;D.;et. al.;Haruta I. et. al.;弘田克彦
  • 通讯作者:
    弘田克彦
The essentiality and involvement of Streptococcus intermedius histone-like DNA-binding protein in bacterial viability and normal growth
  • DOI:
    10.1111/j.1365-2958.2008.06232.x
  • 发表时间:
    2008-06-01
  • 期刊:
  • 影响因子:
    3.6
  • 作者:
    Liu, Dali;Yumoto, Hiromichi;Miyake, Yoichiro
  • 通讯作者:
    Miyake, Yoichiro
A possible role of histone-like DNA-binding protein of Streptococcus intermedius in the pathogenesis of bile duct damage in primary biliary cirrhosis
  • DOI:
    10.1016/j.clim.2008.01.010
  • 发表时间:
    2008-05-01
  • 期刊:
  • 影响因子:
    8.6
  • 作者:
    Haruta, Ikuko;Kikuchi, Ken;Shiratori, Keiko
  • 通讯作者:
    Shiratori, Keiko
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HIROTA Katsuhiko其他文献

HIROTA Katsuhiko的其他文献

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{{ truncateString('HIROTA Katsuhiko', 18)}}的其他基金

Molecular characterization of the pathogenic factors of oral streptococci involved in autoimmune disease
自身免疫性疾病相关口腔链球菌致病因子的分子特征
  • 批准号:
    24592833
  • 财政年份:
    2012
  • 资助金额:
    $ 2.4万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The characterization of DNA-binding protein from Streptococcus intermediusand elucidate its virulence mechanism
中间链球菌 DNA 结合蛋白的表征并阐明其毒力机制
  • 批准号:
    14571788
  • 财政年份:
    2002
  • 资助金额:
    $ 2.4万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
A study Of ora| streptococcal histone-like protein and virulence mechanism
奥拉研究|
  • 批准号:
    12671827
  • 财政年份:
    2000
  • 资助金额:
    $ 2.4万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Immunological analysis of a cell surface antigen by a monoclonal antibody SNH-3 in oral streptococci
单克隆抗体 SNH-3 对口腔链球菌细胞表面抗原的免疫分析
  • 批准号:
    06672059
  • 财政年份:
    1994
  • 资助金额:
    $ 2.4万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Simple and Rapid Identification of the Mutans Group of Streptococci by Enzyme Immunoassay using Monoclonal Antibodies
使用单克隆抗体通过酶免疫分析简单快速地鉴定链球菌变形菌群
  • 批准号:
    04671266
  • 财政年份:
    1992
  • 资助金额:
    $ 2.4万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

相似海外基金

Abrogating human CD59 activity for antibody-based cancer therapy
消除人类 CD59 活性以进行基于抗体的癌症治疗
  • 批准号:
    8009892
  • 财政年份:
    2010
  • 资助金额:
    $ 2.4万
  • 项目类别:
Abrogating human CD59 activity for antibody-based cancer therapy
消除人类 CD59 活性以进行基于抗体的癌症治疗
  • 批准号:
    7786901
  • 财政年份:
    2010
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    $ 2.4万
  • 项目类别:
RECEPTOR MEDIATED EFFECT OF INTERMEDILYSIN ON HUMAN POLYMORPHONUCLEAR LYMPHOCYTE
中间溶素对人多形核淋巴细胞受体介导的作用
  • 批准号:
    7959342
  • 财政年份:
    2009
  • 资助金额:
    $ 2.4万
  • 项目类别:
RECEPTOR MEDIATED EFFECT OF INTERMEDILYSIN ON HUMAN POLYMORPHONUCLEAR LYMPHOCYTE
中间溶素对人多形核淋巴细胞受体介导的作用
  • 批准号:
    7725293
  • 财政年份:
    2008
  • 资助金额:
    $ 2.4万
  • 项目类别:
RECEPTOR MEDIATED EFFECT OF INTERMEDILYSIN ON HUMAN POLYMORPHONUCLEAR LYMPHOCYTE
中间溶素对人多形核淋巴细胞受体介导的作用
  • 批准号:
    7609733
  • 财政年份:
    2007
  • 资助金额:
    $ 2.4万
  • 项目类别:
Regulation of pathogenicity by the heat shock chaperone and the protease in streptococci
链球菌中热休克伴侣和蛋白酶的致病性调节
  • 批准号:
    19590449
  • 财政年份:
    2007
  • 资助金额:
    $ 2.4万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular mechanism of human-specific infection by an oral streptococcus, Streptococcusintermedius
口腔链球菌中间链球菌人类特异性感染的分子机制
  • 批准号:
    18592004
  • 财政年份:
    2006
  • 资助金额:
    $ 2.4万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
A Novel Cholesterol-Dependent Cytolysin Receptor
一种新型胆固醇依赖性溶细胞素受体
  • 批准号:
    7172320
  • 财政年份:
    2005
  • 资助金额:
    $ 2.4万
  • 项目类别:
A Novel Cholesterol-Dependent Cytolysin Receptor
一种新型胆固醇依赖性溶细胞素受体
  • 批准号:
    7324132
  • 财政年份:
    2005
  • 资助金额:
    $ 2.4万
  • 项目类别:
Dynamic structure of intermedilysin : Analysis of membrane binding region
intermedilysin 的动态结构:膜结合区域分析
  • 批准号:
    15590098
  • 财政年份:
    2003
  • 资助金额:
    $ 2.4万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
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