LXRα激动剂通过NF-κB途径抑制巨噬细胞NLRP3炎症小体活化导致成熟IL-1β升高

发布时间：2018-06-01 05:36

本文选题：NLRP炎症小体 + LXRα激动剂　；参考：《中国动脉硬化杂志》2015年01期

【摘要】：目的探讨肝X受体α(LXRα)激动剂对巨噬细胞中Nod样受体蛋白3(NLRP3)炎症小体活化导致成熟白细胞介素1β(IL-1β)水平升高的影响及其机制,为探索同时具有抗炎和调脂能力的防治动脉粥样硬化药物新靶点提供实验支持。方法 THP-1细胞经佛波酯活化成为人源性巨噬细胞,在培养基中加入胆固醇晶体(1μg/L)为模型组,其它各组在模型组基础上分别加入高剂量(30μmol/L)、中剂量(10μmol/L)、低剂量(3.3μmol/L)的LXRα激动剂GW3965以及GW3965 10μmol/L+GGPP 10μmol/L、GGPP 10μmol/L、GW3965 10μmol/L+ABCA1抗体(1∶200)、GW3965 10μmol/L+载脂蛋白E抗体(1∶200),48 h后提取总RNA、总蛋白、核蛋白和培养基蛋白。利用real-time PCR和Western blot对相应指标的mRNA和蛋白水平进行检测。结果模型组成熟IL-1β蛋白水平、NLRP3和Caspase-1的mRNA和蛋白水平与对照组有显著差异(P0.05);与模型组相比,GW3965中、高剂量组上述指标均有显著减低(P0.05),LXRα抑制剂GGPP能显著抑制GW3965的作用(P0.05),载脂蛋白E抗体及ABCA1抗体均对GW3965中剂量的活性无显著影响,单独使用GGPP处理的细胞各项指标与模型组无显著差异。结论 LXRα激动剂能够显著抑制巨噬细胞模型中由胆固醇晶体激活NLRP3炎症小体导致的IL-1β水平升高,且此作用与抑制核因子κB(NF-κB)信号通路有关。
[Abstract]:Objective to investigate the effect of liver X receptor 伪 luciferase (LXR 伪) agonist on the activation of Nod like receptor protein 3 (NLRP3) inflammatory bodies in macrophages and its mechanism. To provide experimental support for exploring new targets of anti-inflammatory and lipid-regulating drugs for prevention and treatment of atherosclerosis. Methods THP-1 cells were activated by phorbol ester to form human macrophages. Cholesterol crystals (1 渭 g / L) were added to the culture medium as model group. The other groups added 30 渭 mol 路L ~ (-1 / L) of LXR 伪 agonist GW3965 and 10 渭 mol / L GW3965 10 渭 mol 路L ~ (-1 / L) GW3965 10 渭 mol / L GGGPP 10 渭 mol 路L ~ (-1) GW3965 10 渭 mol/L ABCA1 antibody 1: 200GW3965 10 渭 mol/L Apolipoprotein E antibody for 48 h to extract total RNAs, total protein. Nuclear protein and medium protein. Real-time PCR and Western blot were used to detect the mRNA and protein levels. Results the mRNA and protein levels of NLRP3 and Caspase-1 in the model group were significantly different from those in the control group (P 0.05), and those in the model group were higher than those in the model group. In the high dose group, the above indexes could significantly reduce the effect of P0.05LXR 伪 inhibitor GGPP on the inhibition of GW3965. Apolipoprotein E antibody and ABCA1 antibody had no significant effect on the activity of GW3965. There was no significant difference between the cells treated with GGPP alone and the model group. Conclusion LXR 伪 agonist can significantly inhibit the increase of IL-1 尾 level induced by cholesterol crystal activated NLRP3 inflammatory corpuscles in macrophage model, and this effect is related to the inhibition of NF-魏 B signaling pathway.
【作者单位】：中国人民解放军第三军医大学药学院药物研究所;
【基金】：国家自然科学基金(81102448)
【分类号】：R965

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