PATHOGENESIS OF LYME NEUROBORRELIOSIS IN THE RHESUS MONKEY: STUDIES IN VITRO

恒河猴莱姆病神经疏螺旋体病的发病机制:体外研究

基本信息

  • 批准号:
    8358082
  • 负责人:
  • 金额:
    $ 3.72万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-05-01 至 2012-04-30
  • 项目状态:
    已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Lyme neuroborreliosis (LNB) manifests in 10-15% of Lyme disease patients that go untreated. We hypothesized that the Lyme disease spirochete Borrelia burgdorferi (Bb) induces inflammatory mediators in glial cells that contribute to glial and neuronal damage, resulting in the pathogenesis of LNB. Here we evaluate the role of inflammation in mediating apoptosis of oligodendrocytes (OLGs), the myelin producing glial cells in the brain, as induced by Bb, by using the anti-inflammatory drug dexamethasone. We evaluated the potential of live Bb to elicit inflammatory mediators in in vitro differentiated cultures of human MO3.13 OLGs by measuring the levels of immune mediators in culture supernatants using Multiplex ELISA assays. Concomitant apoptosis was quantified in these cultures by the in situ TUNEL assay. The above phenomena were evaluated after 48 hours of stimulation with Bb in the presence and absence of various concentrations of the anti-inflammatory drug dexamethasone. Bb induced significantly enhanced levels of the cytokine IL-6 and the chemokines IL-8 and CCL2 (MCP-1) as compared to basal levels in OLGs. These Bb-induced cultures also showed significantly elevated levels of apoptosis as compared to medium controls. Bb induced inflammatory mediators and apoptosis in OLGs in a dose dependent manner. Dexamethasone significantly reduced both the levels of immune mediators as well as apoptosis as induced by Bb when used at lower concentrations (5 and 15 micro molar). Dexamethasone modulates the levels of inflammatory mediators and concomitant apoptosis induced by the Lyme disease spirochete Bb in OLGs, suggesting that the inflammatory response elicited in OLGs by Bb contributes to their apoptotic cell death. As OLGs are vital for the functioning and survival of neurons, the inflammation and subsequent apoptosis of OLGs induced by Bb could contribute to the pathogenesis of LNB.
这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的, 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量, 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 未经治疗的莱姆病患者中,有10%-15%表现为莱姆病患者患有莱姆病。我们推测莱姆病螺旋体伯氏疏螺旋体(BB)诱导胶质细胞中的炎症介质,从而导致神经胶质细胞和神经元的损伤,从而导致LNB的发病。在这里,我们通过使用抗炎药物地塞米松来评估炎症在介导脑组织少突胶质细胞(OLGs)凋亡中的作用。少突胶质细胞是脑内产生髓鞘的胶质细胞,由BB诱导。我们通过多重酶联免疫吸附试验检测培养上清液中免疫介质的水平,评价活体BB在人MO3.13 OLG体外分化培养中诱导炎性介质的能力。用原位末端标记法对这些培养物中伴随的细胞凋亡进行定量。在不同浓度抗炎药地塞米松存在和不存在的情况下,用BB刺激48h后对上述现象进行评估。BB诱导的细胞因子IL-6、趋化因子IL-8和CCL2(MCP-1)水平显著高于基础水平。与培养液对照组相比,这些BB诱导的培养物的细胞凋亡率也显著升高。BB以剂量依赖方式诱导炎性介质和细胞凋亡。地塞米松在较低浓度(5微摩尔和15微摩尔)时显著降低BB诱导的免疫介质水平和细胞凋亡。地塞米松对莱姆病螺旋体BB诱导的OLG炎症介质水平及伴随的细胞凋亡具有调节作用,提示BB诱导的炎症反应参与了OLG的细胞凋亡。由于OLGs对神经元的功能和生存至关重要,BB诱导的OLGs的炎症和随后的凋亡可能参与了LNB的发病。

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

MARIO TOMAS PHILIPP其他文献

MARIO TOMAS PHILIPP的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('MARIO TOMAS PHILIPP', 18)}}的其他基金

PATHOGENESIS OF LYME NEUROBORRELIOSIS: STUDIES EX VIVO & IN VIVO
莱姆病神经疏螺旋体病的发病机制:离体研究
  • 批准号:
    8358068
  • 财政年份:
    2011
  • 资助金额:
    $ 3.72万
  • 项目类别:
A RHESUS MACAQUE MODEL OF STREPTOCOCCUS PNEUMONIAE CARRIAGE
肺炎链球菌携带的恒河猴模型
  • 批准号:
    8358165
  • 财政年份:
    2011
  • 资助金额:
    $ 3.72万
  • 项目类别:
VECTOR-BORNE DISEASES CORE
媒介传播疾病核心
  • 批准号:
    8358066
  • 财政年份:
    2011
  • 资助金额:
    $ 3.72万
  • 项目类别:
DIAGNOSTIC PARASITOLOGY CORE
诊断寄生虫学核心
  • 批准号:
    8358067
  • 财政年份:
    2011
  • 资助金额:
    $ 3.72万
  • 项目类别:
TICK SALIVA INHIBITS INFLAMMATION IN MONOCYTES STIMULATED WITH B BURGDORFERI
蜱唾液抑制布氏 B 氏菌刺激的单核细胞炎症
  • 批准号:
    8358087
  • 财政年份:
    2011
  • 资助金额:
    $ 3.72万
  • 项目类别:
TICK SALIVA INHIBITS INFLAMMATION IN MONOCYTES STIMULATED WITH B BURGDORFERI
蜱唾液抑制布氏 B 氏菌刺激的单核细胞炎症
  • 批准号:
    8172987
  • 财政年份:
    2010
  • 资助金额:
    $ 3.72万
  • 项目类别:
VECTOR-BORNE DISEASES CORE
媒介传播疾病核心
  • 批准号:
    8172960
  • 财政年份:
    2010
  • 资助金额:
    $ 3.72万
  • 项目类别:
PATHOGENESIS OF LYME NEUROBORRELIOSIS IN THE RHESUS MONKEY: STUDIES IN VITRO
恒河猴莱姆病神经疏螺旋体病的发病机制:体外研究
  • 批准号:
    8172979
  • 财政年份:
    2010
  • 资助金额:
    $ 3.72万
  • 项目类别:
DIAGNOSTIC PARASITOLOGY CORE
诊断寄生虫学核心
  • 批准号:
    8172961
  • 财政年份:
    2010
  • 资助金额:
    $ 3.72万
  • 项目类别:
CHARACTERIZATION OF A MORAXELLA SPECIES THAT CAUSES EPSTAXIS IN MACAQUES
导致猕猴腹泻的莫拉氏菌属物种的特征
  • 批准号:
    8173026
  • 财政年份:
    2010
  • 资助金额:
    $ 3.72万
  • 项目类别:

相似海外基金

Development of Enhanced Anti-inflammatory Blood Mononuclear Cell Therapy for ARDS and Elucidation of the Molecular Mechanism
ARDS增强抗炎血液单核细胞治疗的进展及分子机制的阐明
  • 批准号:
    23K07659
  • 财政年份:
    2023
  • 资助金额:
    $ 3.72万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Exploring therapeutic effects of anti-inflammatory and resolving factors in osteoporosis model mice
探讨抗炎和缓解因子对骨质疏松模型小鼠的治疗作用
  • 批准号:
    23K15705
  • 财政年份:
    2023
  • 资助金额:
    $ 3.72万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Investigation of the relation between age-related estradiol fluctuation and pro-/anti-inflammatory effects in transplant immune response.
研究年龄相关雌二醇波动与移植免疫反应中促/抗炎作用之间的关系。
  • 批准号:
    23K19490
  • 财政年份:
    2023
  • 资助金额:
    $ 3.72万
  • 项目类别:
    Grant-in-Aid for Research Activity Start-up
Non-coating anti-microbial, anti-host protein deposition, anti-inflammatory urinary catheter
无涂层抗菌、抗宿主蛋白沉积、抗炎导尿管
  • 批准号:
    10697567
  • 财政年份:
    2023
  • 资助金额:
    $ 3.72万
  • 项目类别:
Identification and optimization of verapamil as a novel neuroprotective and anti-inflammatory agent for reducing long-term neurological morbidities following organophosphate-induced status epilepticus
维拉帕米作为新型神经保护和抗炎剂的鉴定和优化,用于减少有机磷引起的癫痫持续状态后的长期神经系统发病率
  • 批准号:
    10727765
  • 财政年份:
    2023
  • 资助金额:
    $ 3.72万
  • 项目类别:
Anti-inflammatory Effects of Hydrogen Gas Produced by Gut Microflora in a Mouse Model of ARDS
肠道菌群产生的氢气对 ARDS 小鼠模型的抗炎作用
  • 批准号:
    23K08467
  • 财政年份:
    2023
  • 资助金额:
    $ 3.72万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Knockdown of AdipoR2 Compromises Adiponectin’s Anti-inflammatory Actions by Mainly Promoting a Pro-inflammatory Chemokine and Cytokine Secretory Profile in THP-1 Macrophages
AdipoR2 的敲低主要通过促进 THP-1 巨噬细胞中促炎趋化因子和细胞因子的分泌特征来损害脂联素的抗炎作用
  • 批准号:
    493138
  • 财政年份:
    2023
  • 资助金额:
    $ 3.72万
  • 项目类别:
Elucidation of anti-inflammatory mechanism of surface layer protein of lactic acid bacteria focusing on its interaction with lipopolysaccharide.
阐明乳酸菌表面层蛋白的抗炎机制,重点关注其与脂多糖的相互作用。
  • 批准号:
    23K13905
  • 财政年份:
    2023
  • 资助金额:
    $ 3.72万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
SBIR Phase I: Structure-guided design of anti-inflammatory modulators of protease-activated receptor 1 (PAR1)
SBIR I 期:蛋白酶激活受体 1 (PAR1) 抗炎调节剂的结构引导设计
  • 批准号:
    2223225
  • 财政年份:
    2023
  • 资助金额:
    $ 3.72万
  • 项目类别:
    Standard Grant
Targeting anti-viral and anti-inflammatory responses during ocular HSV-1 infection to prevent vision impairment.
针对眼部 HSV-1 感染期间的抗病毒和抗炎反应,以预防视力障碍。
  • 批准号:
    10651054
  • 财政年份:
    2023
  • 资助金额:
    $ 3.72万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了