HIV-1 infection initiates an inflammatory cascade in human renal tubular epithelial cells
HIV-1 infection initiates an inflammatory cascade in human renal tubular epithelial cells
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DOI：
10.1097/01.qai.0000218353.60099.4f
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发表时间：
2006-05-01
影响因子：
3.6
通讯作者：
Klotman, PE
中科院分区：
文献类型：
--
作者：
Ross, MJ;Fan, C;Klotman, PE
hiv相关性肾病（HIVAN）是hiv感染患者慢性肾衰竭的最常见原因。小管间质炎症是HIVAN组织病理学的重要组成部分。HIVAN的发病机制是肾上皮细胞感染的结果，但细胞对这种感染的反应仍然不清楚。在这些研究中，我们使用寡核苷酸微阵列技术鉴定了一名感染水疱性口炎病毒（假型gag/pol-deleted HIV-1）后三个时间点的HIVAN患者肾小管上皮细胞中的差异表达基因。感染后12和24小时，很少有基因有差异表达。然而，感染三天后，47个基因的表达上调了至少1.8倍。这些细胞对HIV-1表达最显著的反应是产生促炎介质，包括趋化因子、细胞因子和粘附分子。许多上调的基因是白细胞介素6和核因子κ B调控的靶标，这表明这些蛋白在小管上皮细胞对hiv - 1感染的反应中起着核心作用。对HIV-1转基因小鼠肾脏的分析揭示了微阵列研究中发现的许多促炎基因的上调。这些研究为HIV-1感染小管上皮细胞导致小管间质炎症和进行性肾损伤的机制提供了新的见解。
HIV-associated nephropathy (HIVAN) is the most common cause of chronic renal failure in HIV-infected patients. Tubulointerstitial inflammation is a prominent component of the histopathology of HIVAN. The pathogenesis of HIVAN is a result of infection of renal epithelial cells, but the cellular response to this infection remains poorly defined. In these studies, we used oligonucleotide microarrays to identify differentially expressed genes in renal tubular epithelial cells from a patient with HIVAN at three time points after infection with vesicular stomatitis virus-pseudotyped gag/pol-deleted HIV-1. Very few genes were differentially expressed 12 and 24 hours after infection. Three days after infection, however, 47 genes were upregulated by at least 1.8-fold. The most prominent response of these cells to HIV-1 expression was production of proinflammatory mediators, including chemokines, cytokines, and adhesion molecules. Many of the upregulated genes are targets of interleukin 6 and nuclear factor kappa B regulation, suggesting a central role for these proteins in the response of tubular epithelial cells to HIV-I infection. Analysis of kidneys from HIV-1 transgenic mice revealed upregulation of many of the proinflammatory genes identified in the microarray Studies. These studies provide novel insights into the mechanisms by which HIV-1 infection of tubular epithelial cells leads to tubulointerstitial inflammation and progressive renal injury.