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.

该项目的目标是确定神经激肽-1 受体 (NKIR) 在相互作用中的作用 HIV 受体和靶向 NKIR 通路元件的抑制药物之间的相互作用，以阻断或减少 活化单核细胞 (MC) 和单核细胞衍生巨噬细胞 (MDM) 中的 HIV 感染性并分析 NKIR 介导的信号传导的作用以及拮抗剂对脑细胞中 HIV-1 感染的影响，特别是 星形胶质细胞和神经祖细胞。 1）我们将表征激活的NKIR表达 单核细胞/巨噬细胞，并确定差异亚型表达是否影响之间的相互作用 NK1R、HIV 辅助受体 CCR5 和 HIV 感染性。我们将研究活化单核细胞中NKI R的表达 和巨噬细胞以及 CCR5 和 NKIR 之间的细胞相互作用。 [...]4) NKIR 表达于 人多能神经祖细胞及其对 SP 诱导的 NKIR 激活的反应以及 HIV gp120 的作用将得到表征。我们将确定SP和gp120对人类NPC的影响 表型、NKIR 表达和对 CXCL12/SDF-1 的反应，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神经祖细胞的影响 SP 诱导的 NKIR 激活和存在以下情况下对 CXCL12/SDF-1 的反应性 将评估 HIV gp120。