IMMUNOMODULATORY ROLE OF 1,25-DIHYDROXYVITAMIN-D3
IMMUNOMODULATORY ROLE OF 1,25-DIHYDROXYVITAMIN-D3
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DOI：
10.1002/jcb.240490106
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发表时间：
1992-05-01
影响因子：
4
通讯作者：
LEMIRE, JM
中科院分区：
文献类型：
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作者：
LEMIRE, JM
活性维生素D代谢物1，25-二羟基维生素D3[1，25-D3]被认为通过与特定的细胞内受体相互作用促进其许多作用。在单核细胞和活化的淋巴细胞中发现这种受体，使研究人员评估了这种激素在免疫系统中的作用。甾醇以剂量依赖性方式抑制淋巴细胞增殖和免疫球蛋白产生。在分子水平上，1，25-D3抑制IL-2、IFN-γ和GM-CSF的mRNA积累。在细胞水平上，该激素干扰T辅助细胞（T（h））功能，减少T（h）诱导B细胞产生免疫球蛋白，并抑制T（h）克隆体内细胞免疫的被动转移。甾醇促进抑制细胞活性并抑制细胞毒性细胞和NK细胞的产生。当在体内给予1，25-D3时，1，25-D3在预防自身免疫性疾病如实验性自身免疫性脑脊髓炎和鼠狼疮方面特别有效，但其功效受到其高钙作用的限制。合成的维生素D3类似物显示出良好的1，25-D3受体结合，但不太明显的高钙作用，在体内最近增强了自身免疫和移植的激素的免疫抑制特性。
The active vitamin D metabolite 1,25-dihydroxyvitamin D3[1,25-D3] is thought to promote many of its actions through interaction with a specific intracellular receptor. The discovery of such receptors in monocytes and activated lymphocytes has led investigators to evaluate the role of the hormone on the immune system. The sterol inhibits lymphocyte proliferation and immunoglobulin production in a dose-dependent fashion. At a molecular level, 1,25-D3 inhibits the accumulation of mRNA for IL-2, IFN-gamma, and GM-CSF. At a cellular level, the hormone interferes with T helper cell (T(h)) function, reducing T(h)-induction of immunoglobulin production by B cells and inhibiting the passive transfer of cellular immunity by T(h)-Clones in vivo. The sterol promotes suppressor cell activity and inhibits the generation of cytotoxic and NK cells. Class II antigen expression on lymphocytes and monocytes is also affected by the hormone.When given in vivo, 1,25-D3 has been particularly effective in the prevention of autoimmune diseases such as experimental autoimmune encephalomyelitis and murine lupus but its efficacy has been limited by its hypercalcemic effect. Synthetic vitamin D3 analogues showing excellent 1,25-D3-receptor binding but less pronounced hypercalcemic effects in vivo have recently enhanced the immunosuppressive properties of the hormone in autoimmunity and transplantation.