Neurokinin-1 Receptor Expression and Function in Human Macrophages and Brain Perspective on the Role in HIV Neuropathogenesis
Neurokinin-1 Receptor Expression and Function in Human Macrophages and Brain Perspective on the Role in HIV Neuropathogenesis
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DOI：
10.1196/annals.1418.007
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发表时间：
2008-01-01
期刊：
影响因子：
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通讯作者：
Kilpatrick, Laurie E.
中科院分区：
文献类型：
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作者：
Douglas, Steven D.;Lai, Jian-Ping;Kilpatrick, Laurie E.
在成年男性和女性中，P物质(SP)在HIV感染中上调，这是由血浆水平升高所决定的。在HIV感染的单核细胞来源的巨噬细胞和细胞系(如THP-1)中，P物质与HIV之间存在相互作用和双向关系。P物质上调HIV，HIV上调SP蛋白表达。神经激肽-1受体(NK1R)拮抗剂通过下调趋化因子受体CCR5和下调HIV LTR来抑制HIV的感染性。神经激肽-1受体以全长和截短形式表达。全长的NK1R能够发出信号，而截短的NK1R启动趋化因子受体CCR5。在人类尸检的大脑中，全长和截短的NK1R都在几个脑区表达。SP-NK1R相互作用在炎症和感染中具有调节作用。截短和全长NK1R的差异表达具有重要的生物学意义。这些包括受体-受体的相互作用(例如，NK1R-CCR5)；在细胞分化过程中表达的变化(例如，THP-1细胞)；以及区域组织分布的差异(例如，不同大脑区域的差异)。NK1R-SP受体通路是重要的细胞调节通路。
Substance P (SP) is upregulated in HIV infection in adult men and women, as determined by increased plasma levels. There is a reciprocal and bidirectional relationship between substance P and HIV in HIV-infected monocyte-derived macrophages and cell lines (e.g., THP-1). Substance P up-regulates HIV and HIV up-regulates SP protein expression. Neurokinin-1 receptor (NK1R) antagonists inhibit HIV infectivity through downregulation of the chemokine receptor, CCR5, and downregulation of HIV LTR. Neurokinin-1 receptor is expressed in full-length and truncated forms. The full-length NK1R is capable of signaling, whereas the truncated NK1R primes the chemokine receptor CCR5. Both full-length and truncated NK1R are expressed in several brain regions in human autopsy brains. SP-NK1R interactions have regulatory roles in inflammation and infection. The differential expression of truncated and full-length NK1R has important biological consequences. These include receptor-receptor interaction (e.g., NK1R-CCR5); changes in expression during cell differentiation (e.g., THP-1 cells); and differences in regional tissue distribution (e.g., differences in different brain regions). NK1R-SP receptor pathways are important cell regulatory pathways.