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百里香酚和香芹酚对人Jurkat T细胞中细胞因子产生和转录因子活性的调节作用

Modulation of Cytokine Production and Transcription Factors Activities in Human Jurkat T Cells by Thymol and Carvacrol.

作者信息

Gholijani Nasser, Gharagozloo Marjan, Kalantar Fathollah, Ramezani Amin, Amirghofran Zahra

机构信息

Autoimmune Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Department of Immunology, Isfahan University of Medical Sciences, Isfahan, Iran. ; Department of Pediatrics, CR-CHUS, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke,Quebec,Canada.

出版信息

Adv Pharm Bull. 2015 Dec;5(Suppl 1):653-60. doi: 10.15171/apb.2015.089. Epub 2015 Dec 31.

Abstract

PURPOSE

Thymol and carvacrol, two main components of thyme, have shown anti-inflammatory effects. The aim of this study was to assess the effects of these components on Jurkat leukemia cells as an in vitro T cell model and their molecular mechanisms of activity.

METHODS

Cells were cultured in the presence of components and subsequently stimulated with phorbol-12-myristate-13-acetate (PMA)/calcium ionophore for evaluating interleukin (IL)-2 and interferon (IFN)-γ production. The activation of T cell transcription factors that included nuclear factors of activated T cells (NFATs), activator protein-1 (AP-1; c-Jun/c-Fos), and nuclear factor (NF)-κB were examined by Western blot analysis.

RESULTS

Thymol and carvacrol at 25 µg/ml significantly reduced IL-2 levels from 119.4 ± 8pg/ml in control cells treated only with PMA/Calcium ionophore and the solvent to 66.9 ± 6.4pg/ml (thymol) and 32.3 ± 3.6pg/ml (carvacrol) and IFN-γ from 423.7 ± 19.7pg/ml in control cells to 311.9 ± 11.6pg/ml (thymol) and 293.5 ± 16.7pg/ml (carvacrol). Western blot analyses of nuclear extracts showed that the same concentrations of components significantly reduced NFAT-2 to 44.2 ± 2.7% (thymol) and 91.4 ± 2.3% (carvacrol) of the control (p<0.05), and c-Fos to 31.2 ± 6.2% (thymol) and 27.6 ± 3.1% (carvacrol) of the control (p<0.01). No effects on NFAT-1, c-Jun and phospho-NF-κBp65 levels were observed.

CONCLUSION

Thymol and carvacrol could contribute to modulation of T cell activity by reducing IL-2 and IFN-γ production possibly through down regulation of AP-1 and NFAT-2 transcription factors suggesting their potential usefulness for reduction of T cell overactivity in immune-mediated diseases.

摘要

目的

百里香的两种主要成分麝香草酚和香芹酚已显示出抗炎作用。本研究的目的是评估这些成分对作为体外T细胞模型的Jurkat白血病细胞的影响及其活性分子机制。

方法

细胞在成分存在的情况下培养,随后用佛波醇-12-肉豆蔻酸酯-13-乙酸酯(PMA)/钙离子载体刺激,以评估白细胞介素(IL)-2和干扰素(IFN)-γ的产生。通过蛋白质印迹分析检测包括活化T细胞核因子(NFATs)、活化蛋白-1(AP-1;c-Jun/c-Fos)和核因子(NF)-κB在内的T细胞转录因子的活化情况。

结果

25μg/ml的麝香草酚和香芹酚显著降低了仅用PMA/钙离子载体和溶剂处理的对照细胞中IL-2水平,从119.4±8pg/ml降至66.9±6.4pg/ml(麝香草酚)和32.3±3.6pg/ml(香芹酚),并将IFN-γ水平从对照细胞中的423.7±19.7pg/ml降至311.9±11.6pg/ml(麝香草酚)和293.5±16.7pg/ml(香芹酚)。细胞核提取物的蛋白质印迹分析表明,相同浓度的成分显著降低了NFAT-2至对照的44.2±2.7%(麝香草酚)和91.4±2.3%(香芹酚)(p<0.05),以及c-Fos至对照的31.2±6.2%(麝香草酚)和27.6±3.1%(香芹酚)(p<0.01)。未观察到对NFAT-1、c-Jun和磷酸化NF-κBp65水平的影响。

结论

麝香草酚和香芹酚可能通过降低IL-2和IFN-γ的产生,可能通过下调AP-1和NFAT-2转录因子来调节T细胞活性,表明它们在减少免疫介导疾病中T细胞过度活化方面具有潜在用途。

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