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在系统性红斑狼疮小鼠模型中评估1,25 - 二羟基维生素D3对调节性T细胞的影响。

Assessment of 1,25-dihydroxyvitamin D3 effects on Treg cells in a mouse model of systemic lupus erythematosus.

作者信息

Lavi Arab Fahimeh, Rastin Maryam, Faraji Fatemeh, Zamani Taghizadeh Rabe Shahrzad, Tabasi Nafise, Khazaee Mahdieh, Haghmorad Dariush, Mahmoudi Mahmoud

机构信息

Immunology Research Center, School of Medicine, Bu-Ali Research Institute, Mashhad University of Medical Sciences , Mashhad , Iran.

出版信息

Immunopharmacol Immunotoxicol. 2015 Feb;37(1):12-8. doi: 10.3109/08923973.2014.968255. Epub 2014 Oct 16.

Abstract

CONTEXT

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which is characterized by the presence of auto-reactive T cell and anti-ds DNA antibodies. Treg cells are crucial for maintaining immunologic self-tolerance and are shown to be reduced in SLE patients. 1,25-Dihydroxyvitamin D3 has immunomedulatory effects on the immune system and has recently received substantial attention.

OBJECTIVE

In this study we evaluated the effects of 1,25-dihydroxyvitamin D3 on Treg cells and related cytokines in lupus-like induced mice model.

MATERIALS AND METHODS

Female Balb/c mice were divided into four groups: Group one: injected with PBS and Freund's adjuvant; Group two: injected with non-activated chromatin; Group three: Lupus-like disease was induced with activated chromatin; Group four: Mice were initially treated for two weeks with 1,25-dihydroxyvitamin D3 and then lupus-like disease was induced. Group five: Four mice from group one were treated with 1,25-dihydroxyvitamin D3 for two weeks after disease establishment. Ten weeks after the last injection the mice were killed and spleens were studied for Treg percentages and expression of cytokine genes.

RESULTS

We found that treatment with 1,25-dihydroxyvitamin D3 reduces IL-6 and IL-10 mRNA expression and increases TGF-β and Foxp3 mRNA expression levels, and also enhances spleen Treg percentage.

CONCLUSIONS

The remarkable reduction of IL-6 and IL-10 gene expressions, significant enhancement of TGF-β and Foxp3 gene expressions, along with an increase in Treg cell population after oral 1,25-dihydroxyvitamin D3 administration suggest a possible role for this vitamin as a prophylactic supplement in SLE.

摘要

背景

系统性红斑狼疮(SLE)是一种慢性自身免疫性疾病,其特征是存在自身反应性T细胞和抗双链DNA抗体。调节性T细胞(Treg细胞)对于维持免疫自身耐受性至关重要,且在SLE患者中数量减少。1,25-二羟维生素D3对免疫系统具有免疫调节作用,最近受到了广泛关注。

目的

在本研究中,我们评估了1,25-二羟维生素D3对狼疮样诱导小鼠模型中Treg细胞及相关细胞因子的影响。

材料与方法

将雌性Balb/c小鼠分为四组:第一组:注射磷酸盐缓冲液(PBS)和弗氏佐剂;第二组:注射未活化的染色质;第三组:用活化的染色质诱导狼疮样疾病;第四组:小鼠先用1,25-二羟维生素D3治疗两周,然后诱导狼疮样疾病。第五组:在疾病形成后,对第一组的四只小鼠用1,25-二羟维生素D3治疗两周。最后一次注射后十周,处死小鼠,研究脾脏中Treg细胞百分比及细胞因子基因表达。

结果

我们发现,用1,25-二羟维生素D3治疗可降低白细胞介素-6(IL-6)和白细胞介素-10(IL-10)的信使核糖核酸(mRNA)表达,增加转化生长因子-β(TGF-β)和叉头框蛋白3(Foxp3)的mRNA表达水平,还能提高脾脏Treg细胞百分比。

结论

口服1,25-二羟维生素D3后,IL-6和IL-10基因表达显著降低,TGF-β和Foxp3基因表达显著增强,同时Treg细胞数量增加,这表明该维生素可能作为预防性补充剂在SLE中发挥作用。

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