Vitamin D3 and its synthetic analogs inhibit the spontaneous in vitro immunoglobulin production by SLE-derived PBMC
Vitamin D3 and its synthetic analogs inhibit the spontaneous in vitro immunoglobulin production by SLE-derived PBMC
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DOI：
10.1006/clim.2000.4998
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发表时间：
2001-04-01
影响因子：
8.6
通讯作者：
Koeffler, HP
中科院分区：
文献类型：
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作者：
Linker-Israeli, M;Elstner, E;Koeffler, HP
系统性红斑狼疮（SLE）高亲和致病性自身抗体的产生可能是由于异常的免疫调节所致。由于1,25二羟基维生素D-3 （1,25 D-3）具有免疫调节活性，我们研究了1,25 D-3及其类似物HM、V、MC1288和KH1060对SLE: PBMC自身抗体产生和增殖的影响。我们发现，在SLE中，T、B和NK表达维生素D-3受体（VDRs）的比例更高（P分别= 0.034、0.006和0.012）。与1,25 D-3化合物孵育SLE PBMC显著降低增殖、多克隆和抗dsdna IgG的产生，以及CD3(+)/DR+ T和B （CD19(+)）细胞的百分比，同时升高NK （CD16(+)）细胞（P < 0.001）。1,25 D-3类似物比天然化合物更有效：KH1060上调SLE单核细胞CD14表达（P < 0.001），抑制SLE源性B淋巴细胞产生多克隆和抗dsdna IgG，诱导活化的B淋巴细胞凋亡。这些数据表明，125种D-3化合物可以为SLE的临床治疗提供新的方法。(C) 2001学术出版社。
The production of high-affinity pathogenic autoantibodies in systemic lupus erythematosus (SLE) may result from aberrant immune regulation. Since 1,25 dihydroxy vitamin D-3 (1,25 D-3) has immunoregulatory activity, we examined effects of 1,25 D-3 and its analogs HM, V, MC1288, and KH1060 on autoantibody production and proliferation of SLE: PBMC. We found, in SLE, a higher percentage of T, B, and NK expressing vitamin D-3 receptors (VDRs) (P = 0.034, 0.006, 0.012, respectively). Incubating SLE PBMC with 1,25 D-3 compounds significantly reduced proliferation, polyclonal and anti-dsDNA IgG production, and the percentages of CD3(+)/DR+ T and B (CD19(+)) cells, while elevating NK (CD16(+)) cells (P < 0.001). 1,25 D-3 analogs were more potent than the natural compound: KH1060 up-regulated CD14 expression by SLE monocytes (P < 0.001), inhibited polyclonal and anti-dsDNA IgG production by SLE-derived B lymphoblasts, and induced apoptosis of activated B lymphoblasts. These data suggest that 1,25 D-3 compounds can offer novel approaches to the clinical management of SLE. (C) 2001 Academic Press.