1,25-二羟维生素D3增加小鼠T细胞系中Ⅰ型白细胞介素-1受体的表达。

1,25-Dihydroxyvitamin D3 increases type 1 interleukin-1 receptor expression in a murine T cell line.

作者信息

Lacey D L, Erdmann J M, Tan H L

机构信息

Department of Pathology, Jewish Hospital of St. Louis, Missouri 63110.

出版信息

J Cell Biochem. 1993 Jun;52(2):159-70. doi: 10.1002/jcb.240520208.

DOI:10.1002/jcb.240520208

PMID:8366134

Abstract

The biologically active metabolite of vitamin D3, 1,25 (OH)2 D3, exerts important immunoregulatory effects in addition to being a central mediator of calcium/phosphate metabolism. Utilizing an interleukin 1 responsive murine T cell line and 125I-interleukin 1 alpha, we show that 1,25 (OH)2 D3 (5,50 nM) enhanced 125I-interleukin 1 alpha binding up to almost 2-fold over control. This 1,25 (OH)2 D3 effect occurred in a dose-dependent manner and was detectable after 24 h but not before 7 h of culture. Scatchard analysis of 125I-interleukin 1 alpha binding data demonstrated that 1,25 (OH)2 D3 enhanced interleukin 1 receptor number without a significant change in affinity. The biologically less potent metabolite of vitamin D3, 25 (OH) D3, also augmented 125I-interleukin 1 alpha binding but at steroid levels 2-3 log orders greater than 1,25 (OH)2 D3. This observation, combined with the presence of high-affinity 3H-1,25 (OH)2 D3 receptors (88 sites/cell, K = 0.45 nM) in cytosolic extracts, strongly suggests that the nuclear vitamin D receptor mediates this steroid's effect on interleukin 1 receptor expression. Based on the capacity of an anti-type 1 interleukin 1 receptor monoclonal antibody (35F5) to block 1,25 (OH)2 D3-enhanced 125I-interleukin 1 alpha binding, we conclude that this steroid augments type 1 interleukin 1 receptor expression. When combined with interleukin 1, a cytokine that also impacts MD10 interleukin 1 receptor expression, 1,25 (OH)2 D3 enhanced interleukin 1 receptor expression. Northern blots hybridized with a 32P-type 1 interleukin 1 receptor cDNA probe show that 1,25 (OH)2 D3 enhanced type 1 interleukin 1 receptor steady state mRNA levels. Functionally, 1,25 (OH)2 D3 pretreatment augmented the MD10 proliferative response to suboptimal levels of interleukin 1 (< 100 fM interleukin 1 alpha). These findings further support 1,25 (OH)2 D3's role as an immunoregulatory molecule and provides a possible mechanism by which this steroid could potentiate certain immune activities.

摘要

维生素D3的生物活性代谢产物1,25（OH）2D3，除了作为钙/磷代谢的核心介质外，还发挥着重要的免疫调节作用。利用白细胞介素1反应性小鼠T细胞系和125I-白细胞介素1α，我们发现1,25（OH）2D3（5、50 nM）可使125I-白细胞介素1α的结合增强至对照的近2倍。这种1,25（OH）2D3的作用呈剂量依赖性，在培养24小时后可检测到，但在培养7小时之前未检测到。对125I-白细胞介素1α结合数据的Scatchard分析表明，1,25（OH）2D3增加了白细胞介素1受体的数量，而亲和力没有显著变化。维生素D3的生物活性较低的代谢产物25（OH）D3也增加了125I-白细胞介素1α的结合，但所需的类固醇水平比1,25（OH）2D3高2-3个对数级。这一观察结果，结合胞质提取物中高亲和力的3H-1,25（OH）2D3受体（88个位点/细胞，K = 0.45 nM）的存在，强烈表明核维生素D受体介导了这种类固醇对白细胞介素1受体表达的影响。基于抗1型白细胞介素1受体单克隆抗体（35F5）能够阻断1,25（OH）2D3增强的125I-白细胞介素1α结合，我们得出结论，这种类固醇增加了1型白细胞介素1受体的表达。当与白细胞介素1（一种也影响MD10白细胞介素1受体表达的细胞因子）联合使用时，1,25（OH）2D3增强了白细胞介素1受体的表达。用32P-1型白细胞介素1受体cDNA探针杂交的Northern印迹显示，1,25（OH）2D3增强了1型白细胞介素1受体的稳态mRNA水平。在功能上，1,25（OH）2D3预处理增强了MD10对次优水平白细胞介素1（<100 fM白细胞介素1α）的增殖反应。这些发现进一步支持了1,25（OH）2D3作为免疫调节分子的作用，并提供了一种可能的机制，通过该机制这种类固醇可以增强某些免疫活性。