Dietary nucleotides (NTs) have an important role in cellular and humoral immunity, intestinal growth, differentiation and recovery from tissue damage. Nucleosides (NSs) are the best-absorbed chemical form of NTs in the intestinal epithelium. The aim of this study was to evaluate the effects of NSs on the activity and expression of multiple transcription factors (TFs) in Caco-2 cells, as a possible molecular mechanism by which NSs modulate gene expression in human intestinal cells. The effects of NS-supplemented media on human Caco-2 cell proliferation, viability, protein and RNA concentration were determined, and the activity and expression profiles of multiple TFs were analyzed by using an array-based technology. Exogenous NSs did not affect Caco-2 cell proliferation or viability but increased the protein content in cytoplasm and nucleus and the nuclear protein/RNA ratio. The addition of NSs to the media increased the expression and activity of the TFs CCAAT displacement protein (CUX1), v-ets avian erythroblastosis virus E26 oncogene homolog 1 (ETS1) and SMAD family member 2. In contrast, NS addition decreased the expression and activity of the general upstream stimulatory factor 1 (USF1), glucocorticoid receptor (NR3C1), NFKB and tumor protein p53. In conclusion, our results suggest that exogenous NSs affect the expression and activity of several TFs involved in cell growth, differentiation, apoptosis, immune response and inflammation.
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