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黄芪甲苷抑制U937巨噬细胞CCL18表达及其作用机制研究

底雪梅,  袁曜晖,  张超,  高越

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底雪梅, 袁曜晖, 张超, 高越. 黄芪甲苷抑制U937巨噬细胞CCL18表达及其作用机制研究[J]. 药学实践与服务, 2019, 37(1): 32-36,41. doi: 10.3969/j.issn.1006-0111.2019.01.008
引用本文: 底雪梅, 袁曜晖, 张超, 高越. 黄芪甲苷抑制U937巨噬细胞CCL18表达及其作用机制研究[J]. 药学实践与服务, 2019, 37(1): 32-36,41. doi: 10.3969/j.issn.1006-0111.2019.01.008
shu
DI Xuemei, YUAN Yaohui, ZHANG Chao, GAO Yue. Research on the effect and mechanism of astragalus Ⅳ(AS-Ⅳ) on the expression of CCL18 in U937 macrophages[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(1): 32-36,41. doi: 10.3969/j.issn.1006-0111.2019.01.008
Citation: DI Xuemei, YUAN Yaohui, ZHANG Chao, GAO Yue. Research on the effect and mechanism of astragalus Ⅳ(AS-Ⅳ) on the expression of CCL18 in U937 macrophages[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(1): 32-36,41. doi: 10.3969/j.issn.1006-0111.2019.01.008
shu

黄芪甲苷抑制U937巨噬细胞CCL18表达及其作用机制研究

doi: 10.3969/j.issn.1006-0111.2019.01.008
  • 1.

    同济大学附属第一妇婴保健院, 上海 201204

  • 2.

    山东中医药大学药学院, 山东 济南 2503553

  • 3.

    海军军医大学药学院实验教学中心, 上海 200433

基金项目: 上海市科委产学研医结合项目（15DZ1900102）

Research on the effect and mechanism of astragalus Ⅳ(AS-Ⅳ) on the expression of CCL18 in U937 macrophages

  • 1.

    First Maternity and Infant Hospital, Tongji University, Shanghai 201204, China

  • 2.

    School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, China

  • 3.

    Experimental and Teaching Center, School of Pharmacy, Naval Medical University, Shanghai 200433, China

  • 摘要: 目的 研究黄芪甲苷（AS-Ⅳ）抑制组织细胞淋巴瘤细胞U937，刺激巨噬细胞分泌肿瘤促进因子CCL18表达及其作用机制。 方法 考察黄芪甲苷对白细胞介素4（IL-4）刺激巨噬细胞CCL18表达的影响；实时PCR检测CCL18 mRNA表达水平；采用酶联免疫吸附检测（Elisa）法测定CCL18蛋白水平；流式细胞仪检测白细胞介素4受体（IL-4R）的表达水平；Elisa法检测信号传导及转录激活因子6（STAT6）磷酸化水平；采用Z″-LYTETM激酶检测法检测Janus激酶（JAK）活性。 结果 黄芪甲苷能显著抑制IL-4诱导的U937巨噬细胞CCL18表达上调，且呈明显的量效依赖性，但对IL-4受体组成亚基表达影响不显著；黄芪甲苷可抑制STAT6的磷酸化，但作用小于AS1517499；黄芪甲苷可抑制JAK1，JAK3和酪氨酸激酶2（TYK2）的活性。 结论 黄芪甲苷可抑制IL-4刺激的U937巨噬细胞CCL18的表达。其作用途径之一可能是通过抑制JAK激酶活性，引起STAT6的转录活性下调，从而抑制CCL18基因表达。
    Abstract: Objective To investigate the effect and mechanism of astragalus Ⅳ(AS-Ⅳ) on the expression of CCL18 in U937 macrophages. Methods The expression of CCL18 mRNA was detected by real time PCR. The expression of CCL18 protein was assessed by Elisa. The expression of IL-4 receptor was measured by flow cytometry. The STAT6 phosphorylation was measured by Elisa. The activity of JAK kinase was detected by Z″-LYTETM kinase assay. Results AS-Ⅳ significantly down-regulated the expression of CCL18 in U937 macrophages stimulated by IL-4 with a dose-dependent manner. However, AS-Ⅳ had no significant effect on IL-4 receptor subunit expression. The STAT6 phosphorylation was inhibited by AS-Ⅳ, but the effect was less than AS1517499; the activity of JAK1, JAK3 and TYK2 kinase were inhibited by AS-Ⅳ. Conclusion AS-Ⅳ could inhibit the expression of CCL18 in U937 macrophages stimulated by IL-4. One of the suggested mechanisms was due to inhibition of JAK kinase activity, which caused STAT6 transcriptional activity down and inhibited CCL18 gene expression.
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  • 收稿日期:  2018-07-06
  • 修回日期:  2018-12-31

黄芪甲苷抑制U937巨噬细胞CCL18表达及其作用机制研究

doi: 10.3969/j.issn.1006-0111.2019.01.008
  • 1. 同济大学附属第一妇婴保健院, 上海 201204
  • 2. 山东中医药大学药学院, 山东 济南 2503553
  • 3. 海军军医大学药学院实验教学中心, 上海 200433
    • 基金项目:  上海市科委产学研医结合项目（15DZ1900102）
  • 收稿日期: 2018-07-06
  • 修回日期: 2018-12-31

摘要: 目的 研究黄芪甲苷（AS-Ⅳ）抑制组织细胞淋巴瘤细胞U937，刺激巨噬细胞分泌肿瘤促进因子CCL18表达及其作用机制。 方法 考察黄芪甲苷对白细胞介素4（IL-4）刺激巨噬细胞CCL18表达的影响；实时PCR检测CCL18 mRNA表达水平；采用酶联免疫吸附检测（Elisa）法测定CCL18蛋白水平；流式细胞仪检测白细胞介素4受体（IL-4R）的表达水平；Elisa法检测信号传导及转录激活因子6（STAT6）磷酸化水平；采用Z″-LYTETM激酶检测法检测Janus激酶（JAK）活性。 结果 黄芪甲苷能显著抑制IL-4诱导的U937巨噬细胞CCL18表达上调，且呈明显的量效依赖性，但对IL-4受体组成亚基表达影响不显著；黄芪甲苷可抑制STAT6的磷酸化，但作用小于AS1517499；黄芪甲苷可抑制JAK1，JAK3和酪氨酸激酶2（TYK2）的活性。 结论 黄芪甲苷可抑制IL-4刺激的U937巨噬细胞CCL18的表达。其作用途径之一可能是通过抑制JAK激酶活性，引起STAT6的转录活性下调，从而抑制CCL18基因表达。

English Abstract

底雪梅, 袁曜晖, 张超, 高越. 黄芪甲苷抑制U937巨噬细胞CCL18表达及其作用机制研究[J]. 药学实践与服务, 2019, 37(1): 32-36,41. doi: 10.3969/j.issn.1006-0111.2019.01.008
引用本文: 底雪梅, 袁曜晖, 张超, 高越. 黄芪甲苷抑制U937巨噬细胞CCL18表达及其作用机制研究[J]. 药学实践与服务, 2019, 37(1): 32-36,41. doi: 10.3969/j.issn.1006-0111.2019.01.008
shu
DI Xuemei, YUAN Yaohui, ZHANG Chao, GAO Yue. Research on the effect and mechanism of astragalus Ⅳ(AS-Ⅳ) on the expression of CCL18 in U937 macrophages[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(1): 32-36,41. doi: 10.3969/j.issn.1006-0111.2019.01.008
Citation: DI Xuemei, YUAN Yaohui, ZHANG Chao, GAO Yue. Research on the effect and mechanism of astragalus Ⅳ(AS-Ⅳ) on the expression of CCL18 in U937 macrophages[J]. Journal of Pharmaceutical Practice and Service, 2019, 37(1): 32-36,41. doi: 10.3969/j.issn.1006-0111.2019.01.008
shu

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