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

Abstract

BackgroundVitamin 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.ResultsWe 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.ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3635-4) contains supplementary material, which is available to authorized users.

Multifaceted remodeling by vitamin C boosts sensitivity of Mycobacterium tuberculosis subpopulations to combination treatment by anti-tubercular drugs

“…Our findings have led to the evolution of vit C-based axenic and intracellular infection models that offer unique advantages over existing set ups: the coexistence of non-replicating/slowly growing/VBNC bacteria and replicating organisms provide opportunities to screen for compounds/combinations with vit C that are effective against these diverse subpopulations, a scenario that prevails in vivo. We showed recently by expression profiling of THP-1 cells that vit C boosts host immune defense functions [83] . Taken together with the present findings, vit C can be seen to modulate two key determinants of TB drug efficacy, namely host factors and antibiotic tolerance in bacteria.…”

Vitamin B and Vitamin C Affect DNA Methylation and Amino Acid Metabolism in Mycobacterium bovis BCG

“…However, despite transcriptomics and proteomics efforts have been studied (Shiloh et al, 2008;Mishra and Sarkar, 2015;Batra et al, 2017;Martini et al, 2019), the effect of vitamin treatment on Mtb metabolomics and gene methylation remains poorly understood. DNA methylation and transcriptional regulation are tightly related and play an important role in the epigenetics of living organisms, whereas vitamins have an anti-tuberculosis effect.…”