Genome-wide expression profiling establishes novel modulatory roles of vitamin C in THP-1 human monocytic cell line.
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.
Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, 110029, India.
Sakshi Dhingra
SD
Batra
Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, 110029, India.
Malobi
M
Nandi
Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, 110029, India.
Kriti
K
Sikri
Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, 110029, India. jstyagi@aiims.edu.
Jaya Sivaswami
JS
Tyagi
D001205:Ascorbic Acid / Q000378:metabolism*; D002460:Cell Line; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D005810:Multigene Family / Q000235:genetics
D001205:Ascorbic Acid
Gene expression; Macrophages; Microarray; THP-1; Vitamin C