INTERMEDIATE FILAMENT EXPRESSION IN ASTROCYTES

星形胶质细胞中的中间丝表达

• 批准号: 8358123
• 负责人: ANDREW G MACLEAN
• 金额: $ 5.78万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/8358123
• 关键词: Astrocytes; Blood - brain barrier anatomy; Brain; CCL7 gene; Cells; Development; Encephalitis; Funding; Glial Fibrillary Acidic Protein; Grant; Inflammatory; Intermediate Filaments; Mediator of activation protein; National Center for Research Resources; Neurons; Neuropathogenesis; Peripheral; Primates; Principal Investigator; Production; Reporting; Research; Research Infrastructure; Resources; SIV; Source; Stimulus; Time; United States National Institutes of Health; Vascular Cell Adhesion Molecule-1; Viral; catalyst; chemokine; cost; cytokine; in vitro Model; macrophage; migration; monocyte; neurotrophic protein S100beta; peripherin

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. We have previously reported that a number of astrocytes can express VCAM-1 and peripherin, an intermediate filament normally found in peripheral neurons. We have also shown that MCP-3 is upregulated close to the blood-brain barrier at the same time. Our hypothesis was that these astrocytes had been activated by viral-infected cells and were a catalyst for the development of encephalitis. Using ex vivo and in vitro models, we examined the timing of increased expression of peripherin in astrocytes, and the concomitant secretion of chemokines. Astrocytes had decreased GFAP expression coincident with increased peripherin. At this time, they were also actively secreting the chemokine MCP-3. This chemokine is important for monocyte migration into brain and the concomitant disruption of the BBB. Thus, MCP-3 is important in neuropathogenesis. It was noted that astrocytes also had increased expression of S100b protein following incubation with SIV infected macrophages. "Cold chase" studies revealed that astrocytes have the capacity to revert to their native state of low peripherin with high GFAP intermediate filaments and low expression of inflammatory cytokines / chemokines. Thus, the inflammatory stimulus is necessary and sufficient for the production of mediator the leads to BBB disruption. Astrocytes have a plasticity of expression of this and other intermediate filaments. This coincides with the synthesis and secretion of biologically relevant chemokines for the development of encephalitis and disruption of the blood-brain barrier.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 我们以前已经报道说，许多星形胶质细胞可以表达VCAM-1和外围蛋白，这是一种通常在外周神经元中发现的中间丝。我们还表明，MCP-3同时靠近血脑屏障。我们的假设是这些星形胶质细胞已被病毒感染的细胞激活，并且是脑炎发育的催化剂。使用离体和体外模型，我们检查了外围蛋白在星形胶质细胞中增加表达增加的时间，以及趋化因子的伴随分泌。星形胶质细胞与周围蛋白增加的GFAP表达降低。目前，他们还积极分泌趋化因子MCP-3。该趋化因子对于单核细胞迁移到大脑和BBB的伴随破坏很重要。因此，MCP-3在神经病发生中很重要。值得注意的是，在与SIV感染的巨噬细胞孵育后，星形胶质细胞的表达也增加了。 “冷追逐”研究表明，星形胶质细胞具有高GFAP中间丝和低表达炎症细胞因子 /趋化因子 /趋化因子 /趋化因子 /趋化因子 /趋化因子 /趋化因子的低外周状态。因此，炎症刺激对于产生介体的导致BBB破坏是必要且足够的。星形胶质细胞具有表达和其他中间细丝的可塑性。这与生物学相关的趋化因子的合成和分泌相吻合，用于发育脑炎和血脑屏障的破坏。