黄芪甲苷抑制U937巨噬细胞CCL18表达及其作用机制研究
投稿时间:2018-07-06  修订日期:2018-12-31  点此下载全文
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].药学实践杂志,2019,37(1):32~36,41
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作者单位E-mail
底雪梅 同济大学附属第一妇婴保健院, 上海 201204  
袁曜晖 山东中医药大学药学院, 山东 济南 2503553  
张超 山东中医药大学药学院, 山东 济南 2503553  
高越 海军军医大学药学院实验教学中心, 上海 200433 gaoyue2000@hotmail.com 
基金项目:上海市科委产学研医结合项目(15DZ1900102)
中文摘要: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。
中文关键词:黄芪甲苷  巨噬细胞  CCL18  特发性肺纤维化
 
Research on the effect and mechanism of astragalus Ⅳ(AS-Ⅳ) on the expression of CCL18 in U937 macrophages
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.
keywords:astragalus Ⅳ  macrophages  CCL18  idiopathic pulmonary fibrosis
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