Department of Biomedical Sciences and Center for Clinical & Translational Science, Creighton University School of Medicine, Omaha, NE 68178, USA.
Exp Mol Pathol. 2012 Aug;93(1):74-81. doi: 10.1016/j.yexmp.2012.04.004. Epub 2012 Apr 16.
Asthma is one of the most common chronic inflammatory diseases of the airways. Calcitriol exerts its action through Vitamin D receptor (VDR), which is a high affinity nuclear receptor. VDR is a transcription factor that alters the transcription of target genes which are involved in a wide spectrum of biological responses. Lower serum vitamin D levels are associated with airway hyperresponsiveness and increased asthma severity. Prohibitin is a ubiquitously expressed protein localized to the cell and mitochondrial membranes and the nucleus.
HBSMCs were cultured and treated with calcitriol and/or TNF-α. The mRNA and protein expression of prohibitin and VDR were analyzed using qPCR and immunoblotting, respectively. In the in vivo studies, female BALB/c mice were fed with special vitamin D-deficient or 2000IU/kg of vitamin D-supplemented diet for 13weeks. Mouse model of allergic airway inflammation was developed by OVA-sensitization and challenge. The expression pattern of TNF-α, prohibitin and VDR in the lung of OVA-sensitized mice was analyzed using immunofluorescence. Calcitriol significantly increased and TNF-α decreased the protein and mRNA expression of prohibitin and VDR in HBSMCs. There was significantly increased expression of TNF-α and decreased expression of VDR and prohibitin in the lung of vitamin D-deficient mouse model of allergic airway inflammation.
These results suggest that under inflammatory conditions there is decreased expression of VDR resulting in decreased expression of prohibitin, which is a vitamin D target gene. Vitamin D deficiency causes increase in the expression of TNF-α, thereby increasing inflammation and decreases the expression of VDR and prohibitin. Supplementation with vitamin D might reduce the levels of TNF-α, thereby increasing the expression of VDR and prohibitin that could be responsible for reducing allergic airway inflammation.
哮喘是最常见的气道慢性炎症性疾病之一。钙三醇通过维生素 D 受体（VDR）发挥作用，VDR 是一种高亲和力核受体。VDR 是一种转录因子，可改变参与广泛生物反应的靶基因的转录。血清维生素 D 水平降低与气道高反应性和哮喘严重程度增加有关。抑素是一种广泛表达的蛋白质，定位于细胞和线粒体膜以及细胞核。
培养 HBSMCs 并分别用钙三醇和/或 TNF-α处理。使用 qPCR 和免疫印迹分别分析抑素和 VDR 的 mRNA 和蛋白表达。在体内研究中，雌性 BALB/c 小鼠用特殊的维生素 D 缺乏或 2000IU/kg 的维生素 D 补充饮食喂养 13 周。通过 OVA 致敏和激发建立变应性气道炎症的小鼠模型。使用免疫荧光分析 OVA 致敏小鼠肺中 TNF-α、抑素和 VDR 的表达模式。钙三醇显著增加 TNF-α降低 HBSMCs 中抑素和 VDR 的蛋白和 mRNA 表达。在维生素 D 缺乏的变应性气道炎症小鼠模型的肺中，TNF-α的表达显著增加，VDR 和抑素的表达显著降低。
这些结果表明，在炎症条件下，VDR 的表达减少导致维生素 D 靶基因抑素的表达减少。维生素 D 缺乏导致 TNF-α表达增加，从而增加炎症并降低 VDR 和抑素的表达。维生素 D 的补充可能降低 TNF-α水平，从而增加 VDR 和抑素的表达，这可能有助于减轻变应性气道炎症。
