Leukotrienes and blood-brain barrier

白三烯和血脑屏障

基本信息

  • 批准号:
    8640878
  • 负责人:
  • 金额:
    $ 40.59万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-05-15 至 2016-04-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Microbial traversal of the blood-brain barrier is required for the development of central nervous system infection, but the underlying mechanisms remain incompletely understood. The blood-brain barrier is a structural and functional barrier that is formed by brain microvascular endothelial cells and protects the brain from any microorganisms circulating in the blood, but recent studies have shown that meningitis-causing pathogens are able to cross the blood-brain barrier as live organisms. We have developed the in vitro blood-brain barrier model by isolation and cultivation of human brain microvascular endothelial cells (HBMEC). Upon cultivation on collagen-coated Transwell inserts the HBMEC monolayers exhibit morphological and functional properties of tight junction formation and polar monolayer. Our Preliminary Studies revealed that meningitis-causing pathogens traverse the HBMEC monolayers without affecting the HBMEC integrity, as assessed by transendothelial electrical resistance and permeability, and microbial traversal of the HBMEC monolayers involves specific host signal transduction pathways. Our additional Preliminary Studies using pharmacological inhibition and gene deletion suggest for the first time that host 5-lipoxygenase is likely to be involved in microbial traversal of the blood-brain barrier. Leukotrienes are synthesized by 5-lipoxygenase and shown to have pathophysiological roles in respiratory diseases, allergic diseases and cardiovascular diseases, but their role in microbial traversal of the blood-brain barrier has not been explored. Our Preliminary Studies with the receptor antagonists revealed that cysteinyl leukotrienes are likely to be involved in microbial traversal of the blood-brain barrier. The overall aim of this application is to investigate and characterize the host signaling molecules involved in microbial traversal of the blood- brain barrier. The information derived from this application will demonstrate the novel contributions of 5- lipoxygenase and leukotrienes to microbial traversal of the blood-brain barrier.
描述(由申请人提供):中枢神经系统感染的发生需要微生物穿过血脑屏障,但其潜在机制仍不完全清楚。血脑屏障是由脑微血管内皮细胞形成的结构和功能屏障,保护大脑免受血液中循环的任何微生物的影响,但最近的研究表明,脑膜炎病原体能够作为活生物体穿过血脑屏障。本研究通过分离培养人脑微血管内皮细胞(HBMEC),建立了体外血脑屏障模型。在胶原包被的Transwell插入物上培养后,HBMEC单层表现出紧密连接形成和极性单层的形态和功能特性。我们的初步研究表明,脑膜炎引起的病原体穿过HBMEC单层而不影响HBMEC的完整性,如通过跨内皮电阻和渗透性所评估的,并且HBMEC单层的微生物穿过涉及特定的宿主信号转导途径。我们额外的初步研究,使用药理学抑制和基因缺失首次表明,宿主5-脂氧合酶可能参与血脑屏障的微生物穿越。白三烯由5-脂氧合酶合成,并显示在呼吸系统疾病、过敏性疾病和心血管疾病中具有病理生理作用,但其在微生物穿越血脑屏障中的作用尚未被探索。我们对受体拮抗剂的初步研究表明,半胱氨酰白三烯可能参与微生物穿越血脑屏障。本申请的总体目的是研究和表征参与微生物穿越血脑屏障的宿主信号分子。从这个应用程序中获得的信息将证明5-脂氧合酶和白三烯对血脑屏障微生物穿越的新贡献。

项目成果

期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cysteinyl leukotrienes as novel host factors facilitating Cryptococcus neoformans penetration into the brain.
  • DOI:
    10.1111/cmi.12661
  • 发表时间:
    2017-03
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Zhu L;Maruvada R;Sapirstein A;Peters-Golden M;Kim KS
  • 通讯作者:
    Kim KS
Effective Plasmid DNA and Small Interfering RNA Delivery to Diseased Human Brain Microvascular Endothelial Cells
有效的质粒 DNA 和小干扰 RNA 递送至患病人脑微血管内皮细胞
The involvement of SelB in the expression of cytotoxic necrotizing factor 1 in Escherichia coli.
SelB 参与大肠杆菌细胞毒性坏死因子 1 的表达。
  • DOI:
    10.1016/j.febslet.2011.05.012
  • 发表时间:
    2011
  • 期刊:
  • 影响因子:
    3.5
  • 作者:
    Yu,Hao;Kim,KwangSik
  • 通讯作者:
    Kim,KwangSik
Therapeutic development of group B Streptococcus meningitis by targeting a host cell signaling network involving EGFR.
  • DOI:
    10.15252/emmm.202012651
  • 发表时间:
    2021-03-05
  • 期刊:
  • 影响因子:
    11.1
  • 作者:
    Zhu N;Zhang C;Prakash A;Hou Z;Liu W;She W;Morris A;Sik Kim K
  • 通讯作者:
    Sik Kim K
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Kwang S Kim其他文献

Invasion of Intestinal Epithelial Cells In Vitro by Escherichia coli Is Influenced by Microaerophilic Conditions and the Presence of ibe Genes † 890
大肠杆菌在体外对肠上皮细胞的侵袭受微需氧条件和 ibe 基因存在的影响†890
  • DOI:
    10.1203/00006450-199804001-00911
  • 发表时间:
    1998-04-01
  • 期刊:
  • 影响因子:
    3.100
  • 作者:
    Michelle M Pietzak;Julie L Badger;Carol A Wass;Dan W Thomas;Kwang S Kim
  • 通讯作者:
    Kwang S Kim

Kwang S Kim的其他文献

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{{ truncateString('Kwang S Kim', 18)}}的其他基金

Cryptococcal Exploitation of the Blood-Brain Barrier
隐球菌对血脑屏障的利用
  • 批准号:
    10012330
  • 财政年份:
    2020
  • 资助金额:
    $ 40.59万
  • 项目类别:
E. coli penetration of the blood-brain barrier
大肠杆菌穿透血脑屏障
  • 批准号:
    9243956
  • 财政年份:
    2016
  • 资助金额:
    $ 40.59万
  • 项目类别:
Pathogenesis of bacterial meningitis
细菌性脑膜炎的发病机制
  • 批准号:
    9303283
  • 财政年份:
    2016
  • 资助金额:
    $ 40.59万
  • 项目类别:
Discovery of Novel Therapeutics for Fungal Pathogens
真菌病原体新疗法的发现
  • 批准号:
    9393966
  • 财政年份:
    2016
  • 资助金额:
    $ 40.59万
  • 项目类别:
Pathogenesis of bacterial meningitis
细菌性脑膜炎的发病机制
  • 批准号:
    9167645
  • 财政年份:
    2016
  • 资助金额:
    $ 40.59万
  • 项目类别:
E. coli penetration of the blood-brain barrier
大肠杆菌穿透血脑屏障
  • 批准号:
    9034789
  • 财政年份:
    2016
  • 资助金额:
    $ 40.59万
  • 项目类别:
Host factors and bacterial meningitis
宿主因素与细菌性脑膜炎
  • 批准号:
    9028219
  • 财政年份:
    2015
  • 资助金额:
    $ 40.59万
  • 项目类别:
Host factors and bacterial meningitis
宿主因素与细菌性脑膜炎
  • 批准号:
    9270628
  • 财政年份:
    2015
  • 资助金额:
    $ 40.59万
  • 项目类别:
Leukotrienes and blood-brain barrier
白三烯和血脑屏障
  • 批准号:
    8071224
  • 财政年份:
    2010
  • 资助金额:
    $ 40.59万
  • 项目类别:
Leukotrienes and blood-brain barrier
白三烯和血脑屏障
  • 批准号:
    8451256
  • 财政年份:
    2010
  • 资助金额:
    $ 40.59万
  • 项目类别:

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α-连环蛋白及其在粘附连接组装和功能中的结合伙伴
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