Genome-wide expression profiling establishes novel modulatory roles of vitamin C in THP-1 human monocytic cell line.
Genome-wide expression profiling establishes novel modulatory roles of vitamin C in THP-1 human monocytic cell line.
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DOI：
10.1186/s12864-017-3635-4
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发表时间：
2017-03-23
期刊：
影响因子：
4.4
通讯作者：
Tyagi JS
中科院分区：
文献类型：
--
作者：
Batra SD;Nandi M;Sikri K;Tyagi JS
维生素C是一种重要的膳食营养素，它是一种有效的抗氧化剂，自由基清除剂，并在许多酶促反应中作为辅因子发挥作用。维生素C也被认为可以增强巨噬细胞的免疫效应功能，巨噬细胞被认为是应对任何病原体的第一道防线。THP-1细胞系广泛用于研究巨噬细胞功能和分析宿主细胞-病原体相互作用。我们对用100 μM维生素C（生理相关浓度的维生素）处理的THP-1细胞进行了全基因组时间基因表达和功能富集分析。维生素C对THP-1细胞的调节作用通过从8小时开始的基因差异表达来揭示。差异表达基因的数量在最早的时间点即8 h达到峰值，随后时间下降，直到96 h。此外，基于统计学上严格的标准的功能富集分析揭示了一系列功能反应，即“基因表达的调节”、“信号转导”、“细胞周期”、“免疫系统过程"、”cAMP代谢过程“、”胆固醇转运“和”离子稳态“。对THP-1细胞和人皮肤成纤维细胞中VitC介导的基因表达调控数据的比较分析揭示了某些功能过程的重叠，如“转录调节”、“细胞周期”和“细胞外基质组织”，以及THP-1特异性反应，即“基因表达调节”和“离子稳态”。值得注意的是，维生素C在整个时间过程中调节“免疫系统”过程。本研究揭示了生理水平的维生素C对THP-1基因表达的全基因组效应。维生素C在巨噬细胞中影响的多种作用突出了其在维持几种细胞功能的稳态中的作用。本研究为使用维生素C-THP-1细胞模型研究包括感染M.结核病和其他细胞内病原体。本文的在线版本（doi：10.1186/s12864-017-3635-4）包含补充材料，可供授权用户使用。
Vitamin C (vit C) is an essential dietary nutrient, which is a potent antioxidant, a free radical scavenger and functions as a cofactor in many enzymatic reactions. Vit C is also considered to enhance the immune effector function of macrophages, which are regarded to be the first line of defence in response to any pathogen. The THP-1 cell line is widely used for studying macrophage functions and for analyzing host cell-pathogen interactions. We performed a genome-wide temporal gene expression and functional enrichment analysis of THP-1 cells treated with 100 μM of vit C, a physiologically relevant concentration of the vitamin. Modulatory effects of vitamin C on THP-1 cells were revealed by differential expression of genes starting from 8 h onwards. The number of differentially expressed genes peaked at the earliest time-point i.e. 8 h followed by temporal decline till 96 h. Further, functional enrichment analysis based on statistically stringent criteria revealed a gamut of functional responses, namely, ‘Regulation of gene expression’, ‘Signal transduction’, ‘Cell cycle’, ‘Immune system process’, ‘cAMP metabolic process’, ‘Cholesterol transport’ and ‘Ion homeostasis’. A comparative analysis of vit C-mediated modulation of gene expression data in THP-1cells and human skin fibroblasts disclosed an overlap in certain functional processes such as ‘Regulation of transcription’, ‘Cell cycle’ and ‘Extracellular matrix organization’, and THP-1 specific responses, namely, ‘Regulation of gene expression’ and ‘Ion homeostasis’. It was noteworthy that vit C modulated the ‘Immune system’ process throughout the time-course. This study reveals the genome-wide effects of physiological levels of vit C on THP-1 gene expression. The multitude of effects impacted by vit C in macrophages highlights its role in maintaining homeostasis of several cellular functions. This study provides a rational basis for the use of the Vitamin C- THP-1 cell model, to study biochemical and cellular responses to stresses, including infection with M. tuberculosis and other intracellular pathogens. The online version of this article (doi:10.1186/s12864-017-3635-4) contains supplementary material, which is available to authorized users.