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活性维生素 D(骨化三醇)单独及与姜黄素联合对多发性硬化症(MS)患者外周血单个核细胞(PBMC)的免疫调节作用。

Immunoregulatory Effects of the Active Form of Vitamin D (Calcitriol), Individually and in Combination with Curcumin, on Peripheral Blood Mononuclear Cells (PBMCs) of Multiple Sclerosis (MS) Patients.

机构信息

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Iranian Center of Neurological Research, Department of Neurology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Antiinflamm Antiallergy Agents Med Chem. 2024;23(2):138-147. doi: 10.2174/0118715230293847240314073359.

DOI:10.2174/0118715230293847240314073359
PMID:38566376
Abstract

OBJECTIVES

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease affecting the central nervous system. Immune cell subsets, notably T helper (Th) 17 and Th1, exert important roles in MS pathogenesis. Whereas, Treg cells modulate the disease process. Calcitriol, the active form of vitamin D, and curcumin, a bioactive compound derived from turmeric, play immunomodulatory effects relevant to autoimmune disorders, including MS. The objective of this study is to investigate the effects of calcitriol and Curcumin on Peripheral blood mononuclear cells (PBMCs) of individuals with MS.

METHODS

PBMCs from twenty MS patients were isolated, cultured, and exposed to 0.004 μg/mL of calcitriol and 10 μg/mL of curcumin. The cells underwent treatment with singular or combined doses of these components to assess potential cumulative or synergistic immunomodulatory effects. Following treatment, the expression levels of genes and the cellular population of Treg, Th1 and Th17 were evaluated using Real-time PCR and flow cytometry.

RESULTS

Treatment with curcumin and calcitriol led to a significant reduction in the expression levels of inflammatory cytokines and transcription factors related to Th1 and Th17 cells, including , and . Furthermore, the frequency of these cells decreased following treatment. Additionally, curcumin and calcitriol treatment resulted in a significant upregulation of the FOXP3 gene expression and an increase in the frequency of Treg cells.

CONCLUSION

This study demonstrates that curcumin and calcitriol can effectively modulate the inflammatory processes intrinsic to MS by mitigating the expression of inflammatory cytokines by Th1 and Th17 cells while concurrently enhancing the regulatory role of Treg cells. Moreover, the combined treatment of curcumin and calcitriol did not yield superior outcomes compared to single-dosing strategies.

摘要

目的

多发性硬化症(MS)是一种影响中枢神经系统的慢性自身免疫性炎症性疾病。免疫细胞亚群,特别是辅助性 T 细胞(Th)17 和 Th1,在 MS 的发病机制中发挥重要作用。而调节性 T 细胞则调节疾病进程。钙三醇,维生素 D 的活性形式,以及姜黄素,一种源自姜黄的生物活性化合物,在包括 MS 在内的自身免疫性疾病中具有免疫调节作用。本研究旨在探讨钙三醇和姜黄素对多发性硬化症患者外周血单个核细胞(PBMCs)的影响。

方法

分离、培养来自 20 名 MS 患者的 PBMCs,并将其暴露于 0.004μg/mL 的钙三醇和 10μg/mL 的姜黄素中。将细胞用这些成分的单一或联合剂量进行处理,以评估潜在的累积或协同免疫调节作用。治疗后,使用实时 PCR 和流式细胞术评估 Treg、Th1 和 Th17 细胞的基因表达水平和细胞群体。

结果

姜黄素和钙三醇的治疗导致与 Th1 和 Th17 细胞相关的炎症细胞因子和转录因子的表达水平显著降低,包括 、和 。此外,治疗后这些细胞的频率下降。此外,姜黄素和钙三醇治疗导致 FOXP3 基因表达显著上调,并增加 Treg 细胞的频率。

结论

本研究表明,姜黄素和钙三醇可通过减轻 Th1 和 Th17 细胞炎症细胞因子的表达,同时增强 Treg 细胞的调节作用,有效调节 MS 固有的炎症过程。此外,与单一剂量策略相比,姜黄素和钙三醇的联合治疗并未产生更好的效果。

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Mult Scler Relat Disord. 2024 Feb;82:105433. doi: 10.1016/j.msard.2024.105433. Epub 2024 Jan 6.
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Iran J Allergy Asthma Immunol. 2023 Oct 29;22(5):452-467. doi: 10.18502/ijaai.v22i5.13995.
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Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome.
维生素 D 未能降低临床孤立综合征后的多发性硬化症活动度。
Brain. 2024 Apr 4;147(4):1206-1215. doi: 10.1093/brain/awad409.
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Factors regulating the differences in frequency of infiltration of Th17 and Treg of the blood-brain barrier.调节血脑屏障中Th17和Treg浸润频率差异的因素。
Immunogenetics. 2023 Oct;75(5):417-423. doi: 10.1007/s00251-023-01310-y. Epub 2023 Jul 11.
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High-dose vitamin D supplementation in relapsing-remitting multiple sclerosis: a randomised clinical trial.复发缓解型多发性硬化症的大剂量维生素D补充治疗:一项随机临床试验
EClinicalMedicine. 2023 Apr 13;59:101957. doi: 10.1016/j.eclinm.2023.101957. eCollection 2023 May.
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