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中国应用生理学杂志 ›› 2020, Vol. 36 ›› Issue (6): 534-538.doi: 10.12047/j.cjap.5865.2020.113

• 研究论文 • 上一篇    下一篇

即早基因c-fos在THP-1单核巨噬细胞亚型极化中的差异表达*

陈启文1,4, 吴国栋2,4, 颜治云2, 张文成3, 张梅4△   

  1. 1.天津中医药大学研究生院, 天津 301617;
    2.武警后勤学院, 天津 300309;
    3.天津市肝脏胰腺纤维化与分子诊疗实验室, 天津 300162;
    4.武警特色医学中心心内科, 天津 300162
  • 收稿日期:2019-04-18 修回日期:2020-11-19 出版日期:2020-11-28 发布日期:2021-03-15
  • 通讯作者: Tel: 13752035080; E-mail: chyouyou@126.com
  • 基金资助:
    *天津市自然科学基金(16JCZDJC31900)

Differential expression of immediately early gene c-fos in THP-1 macrophage subtype polarization

CHEN Qi-wen1,4, WU Guo-dong2,4, YAN Zhi-yun2, ZHANG Wen-cheng3, ZHANG Mei4△   

  1. 1. Tianjin University of Traditional Chinese Medicine, Tianjin 301617;
    2. Logistics University of Chinese People's Armed Police Force, Tianjin 300309;
    3. Tianjin Key Laboratory of Molecular Diagnosis and Treatment in Hepatic and Pancreatic Fibrosis, Tianjin 300162;
    4. Department of Cardiology, Logistics University of Chinese People's Armed Police Force, Tianjin 300162, China
  • Received:2019-04-18 Revised:2020-11-19 Online:2020-11-28 Published:2021-03-15

摘要: 目的:探讨即早基因c-fos在THP-1巨噬细胞亚型极化过程中的表达变化。方法:运用PMA刺激诱导THP-1单核细胞极化为巨噬细胞,观察c-fos在单核细胞极化过程中的表达变化;在PMA刺激的基础上,分别运用LPS和IL-4诱导THP-1巨噬细胞向M1及M2亚型极化,实时定量PCR及Western blot技术分析刺激24 h时,细胞亚型标记物CD274、CD86和CD163的表达变化,并动态观察诱导极化过程中,c-fos的表达情况。结果:c-fos在PMA刺激THP-1单核细胞分化为巨噬细胞过程中蛋白和mRNA水平显示上调;LPS诱导THP-1巨噬细胞极化为M1型过程中,c-fos蛋白和mRNA水平表达降低,其特异性标记物在24 h呈现出M1型极化的特点(CD86蛋白表达升高,CD274、CD163蛋白表达降低);IL-4诱导THP-1巨噬细胞极化为M2型过程中,c-fos蛋白和mRNA水平表达升高,其特异性标记物在24 h表现出M2型极化的特点(CD86蛋白表达降低,CD274、CD163蛋白表达升高)。结论:c-fos参与了THP-1单核细胞向巨噬细胞极化的过程,并且可能通过抑制巨噬细胞M1亚型形成,促进巨噬细胞向M2亚型极化的作用参与巨噬细胞的亚型极化及其功能调节中。

关键词: C-fos, 动脉粥样硬化, 巨噬细胞, 细胞分化, THP-1细胞

Abstract: Objective: To investigate the expression of immediate early gene c-fos in THP-1 macrophage subtype polarization. Methods: PMA was used to induce the polarization of THP-1 monocytes to macrophages, and the expression of c-fos in the polarization process was observed. After PMA treatment, LPS or IL-4 were used alone to induce the polarization of THP-1 macrophages to the M1 or M2 subtypes. Subsequently, real-time quantitative PCR and western-blot were used to analyze the changes in the expressions of the cell subtype markers CD274, CD86 and CD163. Meanwhile, the expression of c-fos in the polarization process was observed dynamically. Results: The levels of c-fos protein and mRNA expressions were up-regulated during PMA-induced polarization of THP-1 monocytes. The protein and mRNA expressions of c-fos were significantly decreased during the polarization of THP-1 cells into M1 macrophages induced by LPS. The specific markers showed the characteristics of M1 macrophages polarization at 24 h (CD86 protein increased, CD274 and CD163 protein decreased). The protein and mRNA expressions of c-fos were significantly increased during the polarization of THP-1 cells into M2 macrophages induced by IL-4. The specific markers showed the characteristics of M2 macrophages polarization at 24 h (CD86 protein decreased, CD274 and CD163 protein increased). Conclusion: C-fos plays an important role in the polarization of THP-1 monocytes to macrophages. Moreover, it may be involved in the regulation of macrophage subtype polarization, by inhibiting the formation of M1 macrophage and promoting the polarization of macrophages to the M2 subtype.

Key words: C-fos, atherosclerosis, macrophages, cell differentiation, THP-1 cells

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