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| 人参皂苷代谢产物CompoundK抑制TNF-α诱导的人支气管上皮细胞分泌RANTES |
| 李群益1,2△,陈莉3,张留弟1,2△,王轶1,2,钟明康1,2,施孝金1,2* |
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(1. 复旦大学附属华山医院临床药学室, 上海 200040;
2. 复旦大学附属华山医院北院临床药学室, 上海 201907;
3. 徐汇区中心医院药械科, 上海 200031
△共同第一作者
*通信作者) |
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| 摘要: |
| 目的 探讨人参皂苷代谢产物Compound K(CK)对炎症因子TNF-α诱导的人支气管上皮细胞BEAS-2B分泌调节活化正常T细胞表达和分泌趋化因子 (RANTES) 的影响及其机制. 方法 ELISA法测定CK对BEAS-2B细胞上清液中RANTES含量的影响;采用RT-PCR和蛋白质免疫印迹技术检测RANTES mRNA及蛋白的表达情况;采用荧光素酶报告基因系统检测CK对活化蛋白转录因子1(activator protein 1, AP-1)和糖皮质激素受体(glucocorticoid receptor, GR)转录抑制或转录激活的影响;运用GR拮抗剂米非司酮,验证CK对RANTES的抑制效应是否由GR介导. 结果 3~30 μmol/L 的CK抑制了TNF-α诱导的RANTES分泌、mRNA及蛋白水平;CK抑制AP-1的转录激活,在BEAS-2B细胞中激活GR信号通路;并且,CK通过GR抑制了BEAS-2B细胞分泌RANTES. 结论 CK能够抑制炎症因子TNF-α诱导的支气管上皮细胞分泌RANTES,其机制可能与激活GR、抑制AP-1对下游靶基因的调控有关. |
| 关键词: 糖皮质激素受体 人参皂苷类 Compound K 炎症 趋化因子CCL5 细胞因子类 哮喘 |
| DOI：10.3724/SP.J.1008.2015.00722 |
| 投稿时间：2014-12-03修订日期：2015-03-23 |
| 基金项目:国家自然科学基金(81302853),教育部博士点基金(20110071120071). |
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| Ginsenoside metabolite Compound K inhibits TNF-α-induced RANTES secretion in human bronchial epithelial cell line |
| LI Qun-yi1,2△,CHEN Li3,ZHANG Liu-di1,2△,WANG Yi1,2,ZHONG Ming-kang1,2,SHI Xiao-jin1,2* |
(1. Clinical Pharmacy Laboratory, Huashan Hospital, Fudan University, Shanghai 200040, China;
2. Clinical Pharmacy Laboratory, Huashan Hospital (North branch), Fudan University, Shanghai 201907, China;
3. Department of Pharmacy and Instrument, Central Hospital of Xuhui District, Shanghai 200031, China
△Co-first authors.
*Corresponding author) |
| Abstract: |
| Objective To explore the effects of ginsenoside metabolite Compound K (CK) on TNF-α-induced RANTES secretion in human bronchial epithelial cell line BEAS-2B and to elucidate its possible mechanism. Methods BEAS-2B cells were cultured and treated with CK in different dosages, and then the secretion of RANTES in BEAS-2B cells exposed to inflammatory stimuli was measured by ELISA kits. Expressions of RANTES mRNA and protein were detected by RT-PCR and Western blotting analysis, respectively. Reporter gene assay was employed to elucidate the interaction between CK and activator protein 1(AP-1), glucocorticoid receptor (GR). CK antagonist mifepristone was used to observe whether the inhibitory effect of CK against RANTES was mediated by GR. Results TNF-α-induced secretion of RANTES in BEAS-2B was markedly inhibited by CK (3-30 μmol/L). Treatment with CK also reduced RANTES mRNA and protein expression. Reporter gene assays indicated that CK was a GR agonist and could repress TNF-α-induced AP-1 transactivation. The inhibitory effects of CK on RANTES secretion were antagonized by mifepristone, suggesting a pivotal role of GR. Conclusion These results suggest that CK may inhibit TNF-α-induced RANTES secretion in human bronchial epithelial cells, which might be associated with GR pathway activation and AP-1 pathway inhibition. |
| Key words: glucocorticoid receptors ginsenosides Compound K inflammation chemokine CCL5 cytokine asthma |
