Project 1

项目1

• 批准号: 8102896
• 负责人: JOHN H WOLFE
• 金额: $ 16.73万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8102896
• 关键词: Affect; Astrocytes; Biological Assay; CCR5 gene; Cells; Chemokine (C-C Motif) Receptor 5; Chemotaxis; Drug Delivery Systems; Elements; Goals; HIV; HIV Envelope Protein gp120; HIV Receptors; HIV-1; Human; Infection; Length; Ligand Binding; Measures; Neurons; Nuclear Pore Complex; Pathway interactions; Phenotype; Protein Isoforms; Receptor Activation; Role; Substance P Receptor; Surface; TACR1 gene; Testing; Therapeutic Uses; Viral; aprepitant; brain cell; macrophage; monocyte; nerve stem cell; receptor expression; receptor-mediated signaling; response

The goals of this project are to determine the role of neurokinin-1 receptor (NKIR) in the interactions between HIV receptors and inhibitory drugs that target elements of the NKIR pathway to block or reduce HIV infectivity in activated monocytes (MC) and monocyte-derived macrophages (MDM) and to analyze the role of NKIR-mediated signaling and the effects of antagonists on HIV-1 infection in brain cells, specifically astrocytes and neural progenitor cells. 1) We will characterize NKIR expression in activated monocyte/macrophages and determine whether differential isoform expression affects interactions between NK1R, the HIV co-receptor CCR5, and HIV infectivity. We will study NKI R expression in activated monocyte and macrophages as well as cellular interactions between the CCR5 and NKIR. [...] 4) NKIR expression in human multipotential neural progenitor cells and their response to SP-induced NKIR activation and the effect of HIV gp120 will be characterized. We will determine the effects of SP and gp120 on human NPC phenotype, NKIR expression, and response to CXCL12/SDF-1 as measured by assays of proliferation and chemotaxis. The effect of the NKIR antagonist aprepitant on neural progenitor phenotype and responsiveness to CXCL12/SDF-1 under conditions of SP-induced NKIR activation and in the presence of HIV gp120 will be evaluated.

本课题的目的是研究神经激肽-1受体（NKIR）在神经细胞与细胞膜相互作用中的作用 HIV受体和抑制性药物之间的关系，这些药物靶向NKIR途径的元件，以阻断或减少 活化单核细胞（MC）和单核细胞衍生的巨噬细胞（MDM）中的HIV感染性，并分析 NKIR介导的信号传导的作用和拮抗剂对脑细胞中HIV-1感染的影响， 星形胶质细胞和神经祖细胞。1)我们将在活化的细胞中表征NKIR表达， 单核细胞/巨噬细胞之间的相互作用，并确定是否差异亚型表达影响之间的相互作用 NK 1 R，HIV共受体CCR 5和HIV感染性。我们将研究活化的单核细胞中NKI R的表达， 和巨噬细胞以及CCR 5和NKIR之间的细胞相互作用。[...] 4)NKIR表达 人多能神经前体细胞及其对SP诱导的NKIR活化的反应和 HIV gp 120的作用将被表征。我们将研究SP和gp 120对人鼻咽癌细胞的作用 表型、NKIR表达和对CXCL 12/SDF-1的反应，如通过增殖和 趋化性NKIR拮抗剂阿瑞匹坦对神经祖细胞表型和细胞周期的影响 在SP诱导的NKIR活化条件下和在存在 将对HIV gp 120进行评价。