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Abstract Title:

Genome-wide expression profiling establishes novel modulatory roles of vitamin C in THP-1 human monocytic cell line.

Abstract Source:

BMC Genomics. 2017 Mar 23 ;18(1):252. Epub 2017 Mar 23. PMID: 28335738

Abstract Author(s):

Sakshi Dhingra Batra, Malobi Nandi, Kriti Sikri, Jaya Sivaswami Tyagi

Article Affiliation:

Sakshi Dhingra Batra

Abstract:

BACKGROUND: 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.

RESULTS: 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-1specific responses, namely, 'Regulation of gene expression' and 'Ion homeostasis'. It was noteworthy that vit C modulated the 'Immune system' process throughout the time-course.

CONCLUSIONS: 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.

Study Type : Human In Vitro

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Sayer Ji
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