Hanel Andrea, Veldhuizen Cor, Carlberg Carsten
Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
Carbogen Amcis, B.V., Veenendaal, Netherlands.
Front Nutr. 2022 Jul 13;9:910601. doi: 10.3389/fnut.2022.910601. eCollection 2022.
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 (25(OH)D), 25(OH)D and 1α,25-dihydroxyvitamin D (1,25(OH)D). Saturating concentrations of 1,25(OH)D, 25(OH)D and 25(OH)D resulted after 24 h stimulation in a comparable number and identity of target genes, but below 250 nM 25(OH)D and 25(OH)D were largely insufficient to affect the transcriptome. The average EC values of 206 common target genes were 322 nM for 25(OH)D and 295 nM for 25(OH)D being some 600-fold higher than 0.48 nM for 1,25(OH)D. 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 and 25(OH)D were as prominent as to 1,25(OH)D, both vitamin D metabolites may directly control gene expression. In conclusion, at supra-physiological concentrations 25(OH)D and 25(OH)D are equally potent in modulating the transcriptome of PBMCs possibly by directly activating the vitamin D receptor.
人外周血单个核细胞（PBMCs）是一种高度反应性的原代组织，由先天性和适应性免疫细胞组成。在本研究中，我们比较了维生素D代谢产物25-羟基维生素D（25(OH)D）、25(OH)D和1α,25-二羟基维生素D（1,25(OH)D）对PBMCs转录组的调节作用。在24小时刺激后，1,25(OH)D、25(OH)D和25(OH)D的饱和浓度导致了数量相当且种类相同的靶基因，但在250 nM以下，25(OH)D和25(OH)D在很大程度上不足以影响转录组。206个共同靶基因的平均EC值，25(OH)D为322 nM，25(OH)D为295 nM，比1,25(OH)D的0.48 nM高约600倍。靶基因的类型，如初级/次级、直接/间接或上调/下调，对维生素D代谢产物的敏感性没有显著影响，但个别基因可分为高、中、低反应者。由于1α-羟化酶CYP27B1在PBMCs中表达非常低，并且对25(OH)D和25(OH)D的早期（4小时和8小时）转录组反应与对1,25(OH)D的反应一样显著，因此这两种维生素D代谢产物可能直接控制基因表达。总之，在超生理浓度下，25(OH)D和25(OH)D在调节PBMCs转录组方面同样有效，可能是通过直接激活维生素D受体来实现的。
