Treatment with Vitamin D/MOG Association Suppresses Experimental Autoimmune Encephalomyelitis.

Treatment with Vitamin D/MOG Association Suppresses Experimental Autoimmune Encephalomyelitis.
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维生素D/MOG关联治疗可抑制实验性自身免疫性脑脊髓炎。

DOI:
10.1371/journal.pone.0125836
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Sartori A
Sartori A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chiuso-Minicucci F;Ishikawa LL;Mimura LA;Fraga-Silva TF;França TG;Zorzella-Pezavento SF;Marques C;Ikoma MR;Sartori A

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实验性自身免疫性脑脊髓炎(EAE)是研究多发性硬化(MS)的动物模型。考虑到活性维生素D的致耐受作用,我们评估了与活性维生素D相关的髓鞘少突胶质细胞糖蛋白(MOG)在EAE发展中的治疗作用。通过用完全弗氏佐剂乳化的MOG加结核分枝杆菌免疫雌性C57 BL/6小鼠诱导EAE。动物还接受两次腹膜内剂量的百日咳杆菌毒素。免疫后1天,在15天内(第1、3、5、7、9、11、13和15天)每隔一天用0.1 μg 1α,25-二羟基维生素D3(1,25(OH)2D 3)处理小鼠。在第3天和第11天共同施用MOG(150μg)。给予1,25(OH)2D 3或MOG可显着降低EAE发生率和临床评分。当MOG与1,25(OH)2D 3相关时,动物未发生EAE。与EAE对照组相比,来自该组的脾和中枢神经系统(CNS)细胞培养物在用MOG刺激后产生较少的IL-6和IL-17。此外,该处理抑制了脾脏中树突状细胞的成熟,并减少了CNS中的炎症浸润。MOG与1,25(OH)_2D_3的联合作用能控制EAE的发展。
Experimental autoimmune encephalomyelitis (EAE) is an animal model to study multiple sclerosis (MS). Considering the tolerogenic effects of active vitamin D, we evaluated the therapeutic effect of myelin oligodendrocyte glycoprotein (MOG) associated with active vitamin D in EAE development. EAE was induced in female C57BL/6 mice by immunization with MOG emulsified with Complete Freund’s Adjuvant plus Mycobacterium tuberculosis. Animals also received two intraperitoneal doses of Bordetella pertussis toxin. One day after immunization, mice were treated with 0,1μg of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) every other day during 15 days (on days 1, 3, 5, 7, 9, 11, 13 and 15). MOG (150μg) was co-administered on days 3 and 11. The administration of 1,25(OH) 2D3 or MOG determined significant reduction in EAE incidence and in clinical scores. When MOG was associated with 1,25(OH) 2D3 the animals did not develop EAE. Spleen and central nervous system (CNS) cell cultures from this group produced less IL-6 and IL-17 upon stimulation with MOG in comparison to the EAE control group. In addition, this treatment inhibited dendritic cells maturation in the spleen and reduced inflammatory infiltration in the CNS. The association of MOG with 1,25(OH) 2D3 was able to control EAE development.
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