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奥瑞他汀调节人分离淋巴细胞中正常和 Th 刺激情况下 Th/Th/T 平衡、NF-κB 核定位和一氧化氮产生。

Auraptene regulates Th/Th/T balances, NF-κB nuclear localization and nitric oxide production in normal and Th provoked situations in human isolated lymphocytes.

机构信息

Student Research Committee, Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

Inflammation and Inflammatory Diseases Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Phytomedicine. 2018 Apr 1;43:1-10. doi: 10.1016/j.phymed.2018.03.049. Epub 2018 Mar 19.

DOI:10.1016/j.phymed.2018.03.049
PMID:29747740
Abstract

BACKGROUND

Auraptene as member of dietary coumarins, is found in citrus fruits. Former studies have demonstrated its anti-inflammatory and anti-cancer activity.

PURPOSE

The mechanism of action and immune-modulatory property of this compound on human lymphocytes are greatly unknown.

STUDY DESIGN/METHODS: The effect of three concentrations (10, 30 and 90 µM) of auraptene or dexamethasone (0.1 mM) were evaluated on percentage of cell proliferation and nitric oxide (NO) production as well as secretion and gene expression of cytokines, and NF-κB level in PHA-stimulated and non-stimulated lymphocytes.

RESULTS

In non-stimulated cells, all three concentrations of auraptene significantly increased the gene expression index of IL-10 (P < 0.05-0.001). The IFN-γ gene expression index, IFN-γ/IL-4 and IL-10/IL-4 gene expression ratio were significantly increased due to the high concentration (90 µM) of auraptene treatment compared to control group (P < 0.05-0.001). In PHA stimulation, all three concentrations of the extract significantly decreased proliferation, cytokines (IL-4, IL-10 and IFN-γ) and NF-κB level as well as NO production, but IFN-γ/IL-4 and IL-10/IL-4 ratio were significantly increased compared control group (P < 0.05-0.001). Gene expression of IL-10 and IL-4 was decreased but that of IFN-γ as well as FN-γ/IL-4 and IL-10/IL-4 ratio were significantly increased due to all three concentrations of auraptene.

CONCLUSION

The results showed promoting effects of auraptene on T cell subsets toward Th (IFN-γ) and T (IL-10), which suggest its therapeutic value for treatment of Th cells predominant diseases including allergic disease such as asthma and atopic dermatitis as well as cancers.

摘要

背景

作为膳食香豆素的成员之一,佛手柑内酯存在于柑橘类水果中。以前的研究表明其具有抗炎和抗癌活性。

目的

这种化合物对人淋巴细胞的作用机制和免疫调节特性尚不清楚。

研究设计/方法:评估了三种浓度(10、30 和 90µM)佛手柑内酯或地塞米松(0.1mM)对 PHA 刺激和非刺激淋巴细胞中细胞增殖和一氧化氮(NO)产生的百分比、细胞因子分泌和基因表达以及 NF-κB 水平的影响。

结果

在非刺激细胞中,三种浓度的佛手柑内酯均显著增加了 IL-10 的基因表达指数(P<0.05-0.001)。与对照组相比,高浓度(90µM)佛手柑内酯处理显著增加了 IFN-γ 基因表达指数、IFN-γ/IL-4 和 IL-10/IL-4 基因表达比值(P<0.05-0.001)。在 PHA 刺激下,提取物的三种浓度均显著降低了增殖、细胞因子(IL-4、IL-10 和 IFN-γ)和 NF-κB 水平以及 NO 产生,但 IFN-γ/IL-4 和 IL-10/IL-4 比值与对照组相比显著增加(P<0.05-0.001)。由于佛手柑内酯的三种浓度均降低了 IL-10 和 IL-4 的基因表达,但增加了 IFN-γ 以及 IFN-γ/IL-4 和 IL-10/IL-4 比值。

结论

结果表明,佛手柑内酯对 T 细胞亚群向 Th(IFN-γ)和 T(IL-10)的促进作用,提示其在治疗 Th 细胞占主导地位的疾病方面具有治疗价值,包括哮喘和特应性皮炎等过敏性疾病以及癌症。

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