Monash Centre for Health Research and Implementation (MCHRI), School of Public Health and Preventive Medicine, Monash University, 43-51 Kanooka Grove, Clayton, Melbourne, VIC 3168, Australia.
Centre for Chronic Disease, Victoria University, 176 Furlong Road, St Albans, Melbourne, VIC 3021, Australia.
J Steroid Biochem Mol Biol. 2018 Mar;177:216-222. doi: 10.1016/j.jsbmb.2017.07.013. Epub 2017 Jul 18.
Vitamin D has been reported to have anti-inflammatory properties in in vitro and animal studies, which are thought to occur via inhibition of the nuclear factor kappa-B (NFκB) pathway. However, the association between vitamin D and in vivo NFκB activity in humans has not previously been reported. The aim of the present study was to examine the associations between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and NFκB activity in peripheral blood mononuclear cells (PBMCs) as well as plasma inflammatory markers in healthy individuals. We hypothesized that 25(OH)D concentrations would be negatively associated with NFκB activity and pro-inflammatory markers downstream of NFκB, and positively associated with anti-inflammatory markers. We measured circulating 25(OH)D (chemiluminescent immunoassay); anthropometry: body mass index (BMI), waist-to-hip ratio (WHR), and % body fat (dual X-ray absorptiometry); plasma pro- and anti-inflammatory markers: high sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and IL-10 (ELISA); and NFκB activity in PBMCs (DNA-binding assay). Forty-nine participants were included in the study (21M/28F; age=31.6±10.2years (mean±SD); BMI=28.4±4.6kg/m; % body fat=30.2±9.3%). Mean 25(OH)D concentration was 48.2±24.5 nmol/l. There were no differences in 25(OH)D concentrations between genders and no association between 25(OH)D concentrations and age, BMI, or % body fat (all p>0.1). Serum 25(OH)D concentrations were positively associated with NFκB activity in PBMCs (r=0.48, p=0.0008) but not with any of the pro- or anti-inflammatory markers measured (all p>0.1). After adjusting for age, sex, and % body fat, 25(OH)D concentrations remained positively associated with NFκB activity in PBMCs (β=0.55, p<0.0001). Although in-vitro studies suggest that vitamin D inhibits NFκB activity, our novel cross-sectional data from a cohort of healthy individuals suggest that vitamin D may regulate rather than inhibit the NFκB pathway. Large-scale intervention and mechanistic studies are needed to further investigate the effects of vitamin D on NFκB activity in vivo in humans.
维生素 D 已被报道在体外和动物研究中具有抗炎特性，这被认为是通过抑制核因子 kappa-B（NFκB）途径发生的。然而，维生素 D 与人类外周血单个核细胞（PBMC）中 NFκB 活性之间的关联以前尚未报道过。本研究旨在研究健康个体中循环 25-羟维生素 D（25（OH）D）浓度与 PBMC 中 NFκB 活性以及血浆炎症标志物之间的关系。我们假设 25（OH）D 浓度与 NFκB 下游的炎症标志物呈负相关，与抗炎标志物呈正相关。我们测量了循环 25（OH）D（化学发光免疫分析）；人体测量学：体重指数（BMI）、腰臀比（WHR）和体脂百分比（双能 X 射线吸收法）；血浆促炎和抗炎标志物：高敏 C 反应蛋白（hsCRP）、肿瘤坏死因子（TNF）、单核细胞趋化蛋白-1（MCP-1）、白细胞介素-6（IL-6）和白细胞介素-10（ELISA）；以及 PBMC 中的 NFκB 活性（DNA 结合测定）。本研究纳入了 49 名参与者（21 名男性/28 名女性；年龄=31.6±10.2 岁（均值±标准差）；BMI=28.4±4.6kg/m；体脂百分比=30.2±9.3%）。平均 25（OH）D 浓度为 48.2±24.5nmol/l。性别之间的 25（OH）D 浓度没有差异，25（OH）D 浓度与年龄、BMI 或体脂百分比之间也没有关联（均 P>0.1）。血清 25（OH）D 浓度与 PBMC 中的 NFκB 活性呈正相关（r=0.48，P=0.0008），但与所测量的任何促炎或抗炎标志物均无关（均 P>0.1）。在校正年龄、性别和体脂百分比后，25（OH）D 浓度与 PBMC 中的 NFκB 活性仍呈正相关（β=0.55，P<0.0001）。尽管体外研究表明维生素 D 抑制 NFκB 活性，但我们来自健康人群队列的新型横断面数据表明，维生素 D 可能调节而不是抑制 NFκB 途径。需要进行大规模干预和机制研究，以进一步研究维生素 D 对人类体内 NFκB 活性的影响。
