Meehan Terrence F, DeLuca Hector F
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin--Madison, 53706, USA.
Arch Biochem Biophys. 2002 Dec 15;408(2):200-4. doi: 10.1016/s0003-9861(02)00580-5.
The active metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D(3), suppresses autoimmune disease in several animal models including experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. The molecular mechanism of this immunosuppression is at present unknown. While 1alpha,25-dihydroxyvitamin D(3) is believed to function through a single vitamin D receptor, there are reports of other vitamin D receptors as well as a "nongenomic" mode of action. We have prepared the EAE model possessing the vitamin D receptor null mutation and determined if 1alpha,25-dihydroxyvitamin D(3) can suppress this disease in the absence of a functional vitamin D receptor. Vitamin D receptor null mice develop EAE although the incidence rate is one-half that of wild-type controls. The administration of 1alpha,25-dihydroxyvitamin D(3) had no significant effect on the incidence of EAE in the vitamin D receptor null mice, while it completely blocked EAE in the wild-type mice. We conclude that 1alpha,25-dihydroxyvitamin D(3) functions to suppress EAE through the well-known VDR and not through an undiscovered receptor or through a "nongenomic" mechanism.
维生素D的活性代谢产物1α,25 - 二羟基维生素D(3)在包括实验性自身免疫性脑脊髓炎（EAE，一种多发性硬化症模型）在内的多种动物模型中可抑制自身免疫性疾病。目前这种免疫抑制的分子机制尚不清楚。虽然人们认为1α,25 - 二羟基维生素D(3)通过单一的维生素D受体发挥作用，但也有关于其他维生素D受体以及“非基因组”作用模式的报道。我们制备了具有维生素D受体无效突变的EAE模型，并确定在缺乏功能性维生素D受体的情况下1α,25 - 二羟基维生素D(3)是否能抑制这种疾病。维生素D受体无效的小鼠会发生EAE，尽管发病率是野生型对照的一半。给予1α,25 - 二羟基维生素D(3)对维生素D受体无效小鼠的EAE发病率没有显著影响，而它能完全阻断野生型小鼠的EAE。我们得出结论，1α,25 - 二羟基维生素D(3)通过众所周知的维生素D受体发挥抑制EAE的作用，而不是通过未被发现的受体或“非基因组”机制。
