STIMULATION OF MONOCYTIC ENDOTHELIN-1 PRODUCTION BY HIV-1 GP120

HIV-1 GP120 刺激单核细胞内皮素-1 的产生

• 批准号: 3792478
• 负责人: K CLOUSE-STREBEL
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3792478
• 关键词: HIV envelope protein gp120; endothelin; gene expression; human immunodeficiency virus 1; human tissue; infectious encephalitis; macrophage; monocyte; polymerase chain reaction; tissue /cell culture

Monocytes/macrophages play a critical role in the pathogenesis of human immunodeficiency virus (HIV) -infection, both as targets f or virus replication and sources of production of multifunctional cytokines. Endothelins, peptides with potent vasoconstricting activities, originally isolated from endothelial cells, are also produced and secreted by macrophages in a manner similar to that of other cytokines. In an attempt to explore the potential role of endothelins in HIV-infection, we investigated the effect of the HIV-1 envelope glycoprotein, gpl20, on monocytic endothelin-1 production. This glycoprotein has been identified as a potent stimulator of monokines such as TNF-alpha and interleukin-6, which have been implicated as potential mediators of HIV-encephalopathy. We found that gpl20, similar to LPS, stimulates the secretion of endothelin-1 as well as TNF-alpha from macrophages in a concentration-dependent manner. Using reverse transcriptase polymerase chain reaction (RT PCR), we found that circulating monocytes in HIV-infected individuals show a distinct expression of the endothelin-1 gene which is not detectable in healthy controls, indicating chronic activation of this gene in HIV-infection. In addition, cerebral macrophages in patients with HIV-encephalopathy were strongly positive for endothelin. Thus, monocytic endothelins appear to be stimulated during HIV-infection. Their potent vasoactive properties render them potential candidates for mediating alterations in the cerebral perfusion pattern associated with the AIDS dementia complex.

单核/巨噬细胞在人类免疫缺陷的发病机制中起重要作用 免疫缺陷病毒(HIV)-感染，两者都是病毒的目标 多功能细胞因子的复制和生产来源。 内皮素，具有强大的血管收缩活性的多肽，最初 从内皮细胞分离出来的，也是由 巨噬细胞的作用方式与其他细胞因子相似。在一个 为了探索内皮素在HIV感染中的潜在作用，我们 研究了HIV-1包膜糖蛋白gpl20对 单核细胞产生内皮素-1。这种糖蛋白已经被鉴定出来 作为一种有效的单因子刺激因子，如肿瘤坏死因子-α和白介素6， 它们被认为是HIV脑病的潜在介体。 我们发现，gpl20类似于内毒素，能刺激 巨噬细胞分泌的内皮素-1和肿瘤坏死因子-α 浓度依赖方式。使用逆转录酶聚合酶 链式反应(RT-PCR)，我们发现循环中的单核细胞 HIV感染者表现出明显的内皮素-1的表达 在健康对照中检测不到的基因，表明慢性 该基因在HIV感染中的激活。此外，大脑 HIV脑病患者巨噬细胞呈强阳性 用来治疗内皮素。因此，单核细胞内皮素似乎受到了刺激。 在感染艾滋病毒期间。它们强大的血管活性使它们 脑血流灌注改变的潜在介导者 与艾滋病痴呆症相关的模式。