Attenuation of experimental autoimmune encephalomyelitis and nonimmune demyelination by IFN-β plus vitamin B12:: Treatment to modify notch-1/sonic hedgehog balance
Attenuation of experimental autoimmune encephalomyelitis and nonimmune demyelination by IFN-β plus vitamin B12:: Treatment to modify notch-1/sonic hedgehog balance
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DOI：
10.4049/jimmunol.172.10.6418
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发表时间：
2004-05-15
影响因子：
4.4
通讯作者：
Moscarello, MA
中科院分区：
文献类型：
--
作者：
Mastronardi, FG;Min, WX;Moscarello, MA
干扰素-β是脱髓鞘疾病的主要疗法，但其在人类多发性硬化症及其几种动物模型中的作用是不完全的。在这项研究中，我们证明了在脱髓鞘疾病的体内小鼠模型的临床，组织学和实验室参数的显着改善，通过联合治疗与IFN-β加维生素B-12氰钴胺（B12 CN）在非自身免疫性原发性脱髓鞘ND 4（DM 20）转基因，并在急性和慢性实验性自身免疫性脑脊髓炎的SJL小鼠。临床改善（p值< 0.0001）被接近正常的运动功能、星形细胞增多减少和脱髓鞘减少所证实。IFN-β加B12 CN增强体内和体外少突胶质细胞成熟。在体内和体外，Notch-1的表达减少和音刺猬及其受体的表达增强的改变模式与少突胶质细胞的成熟和髓鞘再生一致。IFN-β-B12 CN联合治疗可能有希望用于治疗多发性硬化症。
Interferon-beta is a mainstay therapy of demyelinating diseases, but its effects are incomplete in human multiple sclerosis and several of its animal models. In this study, we demonstrate dramatic improvements of clinical, histological, and laboratory parameters in in vivo mouse models of demyelinating disease through combination therapy with IFN-beta plus vitamin B-12 cyanocobalamin (B12CN) in nonautoimmune primary demyelinating ND4 (DM20) transgenics, and in acute and chronic experimental autoinumme encephalomyelitis in SJL mice. Clinical improvement (p values < 0.0001) was paralleled by near normal motor function, reduced astrocytosis, and reduced demyelination. IFN-beta plus B12CN enhanced in vivo and in vitro oligodendrocyte maturation. In vivo and in vitro altered expression patterns of reduced Notch-1 and enhanced expression of sonic hedgehog and its receptor were consistent with oligodendrocyte maturation andremyelination. IFN-beta-B12CN combination therapy may be promising for the treatment of multiple sclerosis.