基础医学与临床 ›› 2018, Vol. 38 ›› Issue (5): 610-615.

• 研究论文 • 上一篇    下一篇

低氧增强巨噬细胞中脂多糖诱导的IL-1β表达

白瑜珊,焦时宇,曲爱娟   

  1. 首都医科大学
  • 收稿日期:2018-03-13 修回日期:2018-03-20 出版日期:2018-05-05 发布日期:2018-04-28
  • 通讯作者: 曲爱娟 E-mail:aijuanqu@ccmu.edu.cn
  • 基金资助:
    国家自然科学基金;国家自然科学基金;国家自然科学基金;北京市自然科学基金B类重点项目

Hypoxia amplifies lipopolysaccharide-induced IL-1β expression in macrophages

  • Received:2018-03-13 Revised:2018-03-20 Online:2018-05-05 Published:2018-04-28
  • Contact: Aijuan Qu E-mail:aijuanqu@ccmu.edu.cn
  • Supported by:
    National Natural Science Foundation of China;National Natural Science Foundation of China;National Natural Science Foundation of China

摘要: 目的 探讨低氧对巨噬细胞表达IL-1β的作用及可能机制。方法 给予巨噬细胞系RAW264.7常氧(21% O2)、低氧(2% O2)、常氧联合脂多糖(LPS)培养和低氧联合LPS培养,RT-qPCR检测Vegf、Nlrp3和Il1b的mRNA水平,Western blot检测HIF-1α、NLRP3、caspase-1、cleaved caspase-1、Pro-IL-1β和IL-1β的蛋白水平;Vhlfl/fl/Apoe-/-及VhlΔMac/Apoe-/-小鼠腹腔巨噬细胞给予或不给予LPS培养,RT-qPCR检测Vhl、Nlrp3、Il1b和Il6的mRNA水平。结果 与常氧组相比,低氧仅显著升高RAW264.7 Vegf、Nlrp3和Il1b的mRNA水平(P<0.01)。给予LPS培养后,与常氧组相比,低氧可进一步升高LPS诱导的RAW264.7巨噬细胞中NLRP3和IL-1β mRNA及蛋白水平(P<0.01),低氧联合LPS培养不能激活caspase-1,剪切Pro-IL-1β。给予LPS培养后,VhlΔMac/Apoe-/-小鼠腹腔巨噬细胞与Vhlfl/fl/Apoe-/-小鼠相比,Nlrp3、Il1b和Il6的mRNA表达水平升高更显著(P<0.05)。结论 低氧可以放大巨噬细胞中LPS诱导的IL-1β表达。

关键词: 低氧, 低氧诱导因子, 巨噬细胞, IL-1β

Abstract: Objective To investigate the effect of hypoxia on the expression of IL-1β in macrophages. Methods RAW264.7 cells were treated with normoxia (21% O2), hypoxia (2% O2), normoxia (21% O2) following treatment with LPS and hypoxia (2% O2) following treatment with LPS. RT-qPCR was used to detect the mRNA expression of Vegf, Nlrp3 and Il1b. Western blot was used to detect the protein expression of HIF-1α, NLRP3, caspase-1, cleaved caspase-1, Pro-IL-1β and IL-1β. The peritoneal macrophages of Vhlfl/fl/Apoe-/- mice and VhlΔMac/Apoe-/- mice were treated with or without LPS. RT-qPCR was used to detect the mRNA expression of Vhl, Nlrp3, Il1b and Il6. Results Compared with normoxia, hypoxia only significantly increased the mRNA levels of Vegf, Nlrp3 and Il1b in RAW264.7 (P<0.01). Hypoxia augmented the mRNA and protein levels of NLRP3 and IL-1β in RAW264.7 induced with LPS comparing with normoxia (P<0.01). Hypoxia had no effects on the activation of caspase-1 and the subsequent maturation of Pro-IL-1β induced with LPS in RAW264.7. Compared with Vhlfl/fl/Apoe-/- peritoneal macrophages, VhlΔMac/Apoe-/- peritoneal macrophages showed significantly increased mRNA levels of Nlrp3, Il1b and Il6 induced with LPS (P<0.05). Conclusions Hypoxia amplifies lipopolysaccharide-induced IL-1β expression in macrophages.

Key words: hypoxia, hypoxia inducible factor, macrophage, IL-1β

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