Interleukin-2 is one of the targets of 1,25-dihydroxyvitamin D3 in the immune system

Interleukin-2 is one of the targets of 1,25-dihydroxyvitamin D3 in the immune system
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DOI:
10.1016/s0003-9861(02)00082-6
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发表时间:
2002-06-15
影响因子:
3.9
通讯作者:
Cantorna, MT
Cantorna, MT
中科院分区:
生物学3区
文献类型:
--
作者:
Bemiss, CJ;Mahon, BD;Cantorna, MT

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白介素2基因敲除(KO)小鼠会自发出现类似于人类溃疡性结肠炎的炎症性肠病症状,它们被设置为维生素D缺乏(D-)或维生素D充足(D+)或补充1,25-二羟基维生素D-3(1,25D3)。补充1,25-二羟基维生素D3,但不补充维生素D,降低了IL-2KO小鼠的早期死亡率。然而,D-、D+或1,25D3 IL-2 KO小鼠的结肠炎严重程度没有差别。来自D-IL-2KO小鼠的细胞比所有其他小鼠的细胞产生更多的干扰素(干扰素)-γ。Con A诱导的增殖在IL-2KO小鼠中上调,在喂养1,25133的野生型(WT)小鼠中下调。IL-2KO小鼠细胞中所有其他检测到的免疫反应在维生素D状态下没有变化。在体外,加入1,25-二羟基维生素D3显著减少D-和D+WT小鼠细胞中IL-10和干扰素-γ的产生。相反,IL-2KO小鼠细胞中产生的干扰素-γ和IL-10对体外1,25-二羟基维生素D3治疗无效。在缺乏IL-2的情况下,维生素D对抑制结肠炎无效,也不能在体外下调IL-10或干扰素-γ的产生。免疫系统中1,25-二羟基维生素D3的一个靶点是IL-2基因。(C)2002年埃尔塞维尔科学公司(美国)。版权所有。
Interleukin (IL)-2 knockout (KO) mice, which spontaneously develop symptoms of inflammatory bowel disease similar to ulcerative colitis in humans, were made vitamin D deficient (D-) or vitamin D sufficient (D+) or were supplemented with 1,25-dihydroxyvitamin D-3 (1,25D3). 1,25-Dihydroxyvitamin D3 supplementation, but not vitamin D supplementation, reduced the early mortality of IL-2 KO mice. However, colitis severity was not different in D-, D+, or 1,25D3 IL-2 KO mice. Cells from D- IL-2 KO mice produced more interferon (IFN)-gamma than cells from all other mice. Con A-induced proliferation was upregulated in IL-2 KO mice and downregulated in wildtype (WT) mice fed 1,25133. All other measured immune responses in cells from IL-2 KO mice were unchanged by vitamin D status. In vitro addition of 1,25-dihydroxyvitamin D3 significantly reduced the production of IL-10 and IFN-gamma in cells from D- and D+ WT mice. Conversely, IFN-gamma and IL-10 production in cells from IL-2 KO mice were refractory to in vitro 1,25-dihydroxyvitamin D3 treatments. In the absence of IL-2, vitamin D was ineffective for suppressing colitis and ineffective for the in vitro downregulation of IL-10 or IFN-gamma production. One target of 1,25-dihydroxyvitamin D3 in the immune system is the IL-2 gene. (C) 2002 Elsevier Science (USA). All rights reserved.