黄芪甲苷通过抑制CXCR4恢复Th17/Treg平衡,改善慢性阻塞性肺疾病。

IF 2.9 4区 医学 Q3 IMMUNOLOGY
Xiulian Zhang, Xueliang Li, Wei Ma, Fangying Liu, Pinxian Huang, Lei Wei, Li Li, Yechang Qian
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引用次数: 0

摘要

背景:慢性阻塞性肺疾病(Chronic obstructive pulmonary disease, COPD)病死率高,严重威胁人类健康。黄芪甲苷(Astragaloside IV, AS-IV)已被证实可减轻香烟烟雾(CS)引起的肺部炎症,本研究在此基础上重点探讨AS-IV在COPD中的作用机制。方法:观察不同浓度AS-IV对CD4+ T细胞的影响。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基- 2h -四溴唑试验、实时定量聚合酶链反应和Western blot检测CD4+ T细胞活力、T辅助17 (Th17)/调节性T (Treg)标志物和CXCR4在CD4+ T细胞或脾/肺组织中的表达。流式细胞术检测Treg和Th17细胞的比例。采用酶联免疫吸附法测定血清和肺组织中细胞因子的含量。结果:AS-IV浓度超过40µM可抑制CD4+ T细胞活力。在体外,as - iv抑制CXCR4、类视黄醇相关孤儿受体γt (RORγt)、白细胞介素(IL)-17A和Th17细胞的表达,促进叉头盒p3 (Foxp3)、IL-10和Treg细胞的表达,而CXCR4过表达逆转了as - iv的作用。在体内,AS-IV减轻了COPD和cs诱导的小鼠Th17/Treg失衡,减轻了cs诱导的血清和肺组织中IL-10和Foxp3的下调以及血清和肺组织中IL-1β、肿瘤坏死因子α (TNF-α)、IL-6、IL-17A和RORγt的上调。AS-IV减轻了cs诱导的CXCR4上调。AS-IV对小鼠的上述作用被CXCR4过表达所抵消。结论:AS-IV通过阻碍CXCR4来改善COPD,从而恢复Th17/Treg平衡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Astragaloside IV restores Th17/Treg balance via inhibiting CXCR4 to improve chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) has a high fatality rate and poses a great threat to human health. Astragaloside IV (AS-IV) is proven to attenuate cigarette smoke (CS)-induced pulmonary inflammation, based on which this research focuses on the mechanism of AS-IV in COPD.

Methods: To evaluate the effects of AS-IV, CD4+ T cells received different concentrations of AS-IV. CD4+ T cell viability, T helper 17 (Th17)/regulatory T (Treg) markers and CXCR4 expressions in CD4+ T cells or spleen/lung tissues were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, quantitative real-time polymerase chain reaction and Western blot. The proportions of Treg and Th17 cells were assessed by flow cytometry. Enzyme-linked immune sorbent assay was employed to determine cytokine contents in serum and lung tissues.

Results: AS-IV with concentration exceeding 40 µM inhibited CD4+ T cell viability. In vitro, AS-IV suppressed the expressions of CXCR4, retinoid-related orphan receptor γt (RORγt), and interleukin (IL)-17A as well as Th17 cells but promoted the expressions of forkhead box p3 (Foxp3) and IL-10 as well as Treg cells, while CXCR4 overexpression reversed the effects of AS-IV. In vivo, AS-IV alleviated COPD, and CS-induced Th17/Treg imbalance in mice and reduced CS-induced down-regulation of IL-10 in serum and lung tissues and Foxp3 and up-regulation of IL-1β, tumor necrosis factor alpha (TNF-α), IL-6, and IL-17A in serum and lung tissues and RORγt. AS-IV mitigated CS-induced CXCR4 up-regulation. Above effects of AS-IV on mice were offset by CXCR4 overexpression.

Conclusions: AS-IV restores Th17/Treg balance via impeding CXCR4 to ameliorate COPD.

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来源期刊
CiteScore
5.40
自引率
0.00%
发文量
133
审稿时长
4-8 weeks
期刊介绍: The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal. The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome. With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more. Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).
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