AUTHOR=Hanel Andrea , Veldhuizen Cor , Carlberg Carsten 

TITLE=Gene-Regulatory Potential of 25-Hydroxyvitamin D3 and D2

JOURNAL=Frontiers in Nutrition

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.910601

DOI=10.3389/fnut.2022.910601

ISSN=2296-861X

ABSTRACT=<p>Human peripheral blood mononuclear cells (PBMCs) represent a highly responsive primary tissue that is composed of innate and adaptive immune cells. In this study, we compared modulation of the transcriptome of PBMCs by the vitamin D metabolites 25-hydroxyvitamin D<sub>3</sub> (25(OH)D<sub>3</sub>), 25(OH)D<sub>2</sub> and 1α,25-dihydroxyvitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>D<sub>3</sub>). Saturating concentrations of 1,25(OH)<sub>2</sub>D<sub>3</sub>, 25(OH)D<sub>3</sub> and 25(OH)D<sub>2</sub> resulted after 24 h stimulation in a comparable number and identity of target genes, but below 250 nM 25(OH)D<sub>3</sub> and 25(OH)D<sub>2</sub> were largely insufficient to affect the transcriptome. The average EC<sub>50</sub> values of 206 common target genes were 322 nM for 25(OH)D<sub>3</sub> and 295 nM for 25(OH)D<sub>2</sub> being some 600-fold higher than 0.48 nM for 1,25(OH)<sub>2</sub>D<sub>3</sub>. The type of target gene, such as primary/secondary, direct/indirect or up-/down-regulated, had no significant effect on vitamin D metabolite sensitivity, but individual genes could be classified into high, mid and lower responders. Since the 1α-hydroxylase CYP27B1 is very low expressed in PBMCs and early (4 and 8 h) transcriptome responses to 25(OH)D<sub>3</sub> and 25(OH)D<sub>2</sub> were as prominent as to 1,25(OH)<sub>2</sub>D<sub>3</sub>, both vitamin D metabolites may directly control gene expression. In conclusion, at supra-physiological concentrations 25(OH)D<sub>3</sub> and 25(OH)D<sub>2</sub> are equally potent in modulating the transcriptome of PBMCs possibly by directly activating the vitamin D receptor.</p>