NEUROKININ-1 RECEPTOR EXPRESSION IN THE BRAINS OF SIV-INFECTED RHESUS MACAQUES

感染 SIV 的恒河猴大脑中 NEUROKININ-1 受体的表达

• 批准号: 8173056
• 负责人: Steven Daniel Douglas
• 金额: $ 6.18万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173056
• 关键词: Brain; CCR5 gene; Cell surface; Cells; Chemotaxis; Computer Retrieval of Information on Scientific Projects Database; Development; Disease; Dose; Funding; Grant; Immune system; Infection; Inflammation; Institution; Lesion; Link; Macaca mulatta; Mediating; Mediator of activation protein; Mental Depression; Neurologic; Neurons; Neuropeptides; RANTES; Research; Research Personnel; Resources; Role; SIV; Source; Substance P; Substance P Receptor; United States National Institutes of Health; cell type; immunoregulation; macrophage; monocyte; neuropsychiatry; receptor; receptor expression

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recent studies suggest a link between neuropsychiatric disorders and HIV/SIV infection. Most evidence indicates monocytes/macrophages are the primary cell type infected within the CNS and that they contribute to CNS inflammation and neurologic disease. Substance P (SP), a pleotropic neuropeptide implicated in inflammation, depression and immune modulation via interaction with its cognate receptor, the neurokinin 1 receptor (NK1-R), is produced by monocyte/macrophages. While the presence of NK1-R on neurons is well known, its role on cells of the immune system such as monocyte/macrophages is just beginning to emerge. Therefore, we have examined the expression of SP and NK1-R and their relationship to SIVE lesions and SIV-infected cells. These studies demonstrated that the expression of SP and NK1-R is significantly increased in SIVE lesions. acrophages are the principal cell expressing NK1-R in these lesions. All of the SIV-infected macrophages expressed NK1-R. Additionally, we examined the functional role of SP as a proinflammatory mediator of monocyte activation and chemotaxis. The treatment of monocytes with SP elicited changes in cell-surface expression for CCR5 and NK1-R in a dose-dependent manner. Treatment with SP enhanced both SP and CCL5 mediated chemotaxis. Taken together, these observations suggest that the role of SP and NK1-R are important in SIV infection of macrophages and the development of SIVE lesions.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 最近的研究表明，神经精神疾病与HIV/SIV感染之间存在联系。 大多数证据表明，单核细胞/巨噬细胞是中枢神经系统内感染的主要细胞类型，它们会导致中枢神经系统炎症和神经系统疾病。 物质P（SP）是通过与单核细胞/巨噬细胞相互作用与其同源受体神经蛋白1受体（NK1-R）相互作用，与其炎症，抑郁和免疫调节有关的多元神经肽。 尽管NK1-R在神经元上的存在是众所周知的，但它在免疫系统细胞（例如单核细胞/巨噬细胞）中的作用才刚刚开始出现。 因此，我们检查了SP和NK1-R的表达及其与SIVE病变和SIV感染细胞的关系。这些研究表明，SIVE病变中SP和NK1-R的表达显着增加。峰值是在这些病变中表达NK1-R的主要细胞。 所有SIV感染的巨噬细胞均表达NK1-R。 此外，我们研究了SP作为单核细胞激活和趋化性的促炎介质的功能作用。 用SP的单核细胞以剂量依赖性的方式对CCR5和NK1-R的细胞表达表达的变化进行了处理。 用SP增强了SP和CCL5介导的趋化性。 综上所述，这些观察结果表明，SP和NK1-R的作用在巨噬细胞的SIV感染和SIVE病变的发展中很重要。