维生素 D3 通过下调 Toll 样受体改善小鼠模型中单纯疱疹病毒诱导的贝赫切特病样炎症。

Vitamin D3 ameliorates herpes simplex virus-induced Behçet's disease-like inflammation in a mouse model through down-regulation of Toll-like receptors.

机构信息

Laboratory of Cell Biology, Ajou University Institute for Medical Sciences, Suwon, Korea.

出版信息

Clin Exp Rheumatol. 2011 Jul-Aug;29(4 Suppl 67):S13-9. Epub 2011 Sep 27.

Abstract

OBJECTIVES

This study was conducted to understand the role of vitamin D3 through the regulation of Toll like receptors (TLRs) and cytokines in herpes simplex virus-induced Behçet's disease (BD)-like mice.

METHODS

Serum 25-hydroxyvitamin D (1,25(OH)2D3) levels were measured in BD-like mice, as well as virus injected and asymptomatic appearance BD normal mice (BDN). The frequencies of TLRs of peritoneal macrophages were compared by FACS. To determine the effect of vitamin D3 in vitro, peritoneal macrophages were isolated and then incubated with 1,25(OH)2D3. To identify the mechanism of improvement of BD-like symptoms induced by 1,25(OH)2D3, mice were orally administered 1,25(OH)2D3.

RESULTS

The serum 25-hydroxyvitamin D levels in BD-like mice were 12.4 ± 5.4ng/ml, while they were 17.5 ± 7.2ng/ml in BDN mice. The frequency of TLR2 in BD-like mice was 32.91 ± 20.88%, while it was 12.73 ± 7.67% in BDN. The frequency of TLR4 was 26.09 ± 10.20% in BD-like mice and 9.72 ± 5.30% in BDN. In a 72 h culture of peritoneal macrophages in 10-8 M 1,25(OH)2D3, the frequency of TLR2 was 25.0 ± 2.7%, while it was 37.3 ± 5.8% in the control group. The frequency of TLR4 was 18.9 ± 5.3% with 1,25(OH)2D3, while it was 30.3 ± 0.1% in the control group. Treatment with 1,25(OH)2D3 improved the symptoms in six out of 11 BD-like mice and downregulated the frequency of TLR2 and TLR4. Moreover, 1,25(OH)2D3 influenced Interleukin-6 and TNF-alpha expression in the sera of BD-like mice.

CONCLUSIONS

Vitamin D improved BD-like symptoms by down-regulating the expression of TLRs and pro-inflammatory cytokines in in vivo mouse models.

摘要

目的

本研究旨在通过调节 Toll 样受体（TLRs）和细胞因子，了解维生素 D3 在单纯疱疹病毒诱导的贝切特病（BD）样小鼠中的作用。

方法

测量 BD 样小鼠、病毒注射和无症状出现的 BD 正常小鼠（BDN）的血清 25-羟维生素 D（1,25（OH）2D3）水平。通过 FACS 比较腹腔巨噬细胞 TLR 的频率。为了确定维生素 D3 的体外作用，分离腹腔巨噬细胞，然后用 1,25（OH）2D3 孵育。为了确定 1,25（OH）2D3 改善 BD 样症状的机制，通过口服给予 1,25（OH）2D3。

结果

BD 样小鼠血清 25-羟维生素 D 水平为 12.4 ± 5.4ng/ml，BDN 小鼠为 17.5 ± 7.2ng/ml。BD 样小鼠 TLR2 的频率为 32.91 ± 20.88%，BDN 为 12.73 ± 7.67%。TLR4 的频率在 BD 样小鼠中为 26.09 ± 10.20%，在 BDN 中为 9.72 ± 5.30%。在 10-8M 1,25（OH）2D3 培养 72 小时的腹腔巨噬细胞中，TLR2 的频率为 25.0 ± 2.7%，而对照组为 37.3 ± 5.8%。TLR4 的频率为 18.9 ± 5.3%，用 1,25（OH）2D3，而对照组为 30.3 ± 0.1%。用 1,25（OH）2D3 治疗改善了 11 只 BD 样小鼠中的 6 只的症状，并下调了 TLR2 和 TLR4 的频率。此外，1,25（OH）2D3 影响了 BD 样小鼠血清中白细胞介素-6 和肿瘤坏死因子-α的表达。