HIV-1 infection is associated with changes in nuclear receptor transcriptome, pro-inflammatory and lipid profile of monocytes
HIV-1 infection is associated with changes in nuclear receptor transcriptome, pro-inflammatory and lipid profile of monocytes
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DOI：
10.1186/1471-2334-12-274
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发表时间：
2012-10-29
影响因子：
3.7
通讯作者：
Fiorucci, Stefano
中科院分区：
文献类型：
--
作者：
Renga, Barbara;Francisci, Daniela;Fiorucci, Stefano
背景：持续的残留免疫激活和脂质代谢异常是接受高效抗逆转录病毒疗法(HAART)的HIV阳性患者的特征。核受体是一类转录因子，通过基因转录调控参与免疫和代谢功能的调节。为了解HAART治疗前后HIV感染者外周血单核细胞中核受体家族成员的相对丰度。方法：采用实时定量聚合酶链式反应(RT-PCR)技术检测HAART治疗前后HIV感染者外周血单核细胞中FXR、PXR、LXR、VDR、RARA、RXR、PPARα、PPARβ、PPARγ和GR的相对mRNA表达。结果：HIV感染者外周血单核细胞核受体表达模式发生改变，表现为FXR、PXR、PPARα、GR、RARα和RXR的表达显著降低。值得注意的是，在HAART下，核受体的非调控表达没有恢复，并且与单核细胞中支持免疫激活和脂代谢改变的基因的表达改变有关。结论：单核细胞中介导脂代谢和免疫功能相互调节的基因表达发生了变化。本研究结果为HIV感染者的免疫激活和脂质代谢异常提供了一种机制上的解释，并可能导致新的潜在治疗靶点的确定。
Background: Persistent residual immune activation and lipid dysmetabolism are characteristics of HIV positive patients receiving an highly active antiretroviral therapy (HAART). Nuclear Receptors are transcription factors involved in the regulation of immune and metabolic functions through the modulation of gene transcription. The objective of the present study was to investigate for the relative abundance of members of the nuclear receptor family in monocytic cells isolated from HIV positive patients treated or not treated with HAART.Methods: Monocytes isolated from peripheral blood mononuclear cells (PBMC) were used for analysis of the relative mRNA expressions of FXR, PXR, LXR, VDR, RARa, RXR, PPAR alpha, PPAR beta, PPAR gamma and GR by Real-Time polymerase chain reaction (PCR). The expression of a selected subset of inflammatory and metabolic genes MCP-1, ICAM-1, CD36 and ABCA1 was also measured.Results: Monocytes isolated from HIV infected patients expressed an altered pattern of nuclear receptors characterized by a profound reduction in the expressions of FXR, PXR, PPAR alpha, GR, RAR alpha and RXR. Of interest, the deregulated expression of nuclear receptors was not restored under HAART and was linked to an altered expression of genes which supports both an immune activation and altered lipid metabolism in monocytes.Conclusions: Altered expression of genes mediating reciprocal regulation of lipid metabolism and immune function in monocytes occurs in HIV. The present findings provide a mechanistic explanation for immune activation and lipid dysmetabolism occurring in HIV infected patients and could lead to the identification of novel potential therapeutic targets.