铁离子通过ROS-乙酰化P53促进巨噬细胞M1型极化

周赟; 易竹君; 阙克婷; 张震; 刘作金

doi:10.16016/j.1000-5404.201709055

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铁离子通过ROS-乙酰化P53促进巨噬细胞M1型极化

基础医学 | 更新时间：2026-01-09

- 铁离子通过ROS-乙酰化P53促进巨噬细胞M1型极化
- Iron ion polarizes macrophages to M1 subtype through ROS-acetyl-P53
- 第三军医大学学报 2018年40卷第1期页码：45-52
- 作者机构：
  
  400010 重庆, 重庆医科大学第二附属医院肝胆外科
- 作者简介：
  
  [ 刘作金, E-mail: liuzuojin66@163.com LIU Zuojin, E-mail: liuzuojin66@163.com
- 基金信息：
  
  国家自然科学基金面上项目(81470899);国家自然科学基金面上项目(81170442)
- DOI：10.16016/j.1000-5404.201709055
  中图分类号： R329.24;R392.12;R977.5
- 收稿：2017-09-08，
  
  修回：2017-10-19，
  
  纸质出版：2018-01-15
- 稿件说明：
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周赟, 易竹君, 阙克婷, 等. 铁离子通过ROS-乙酰化P53促进巨噬细胞M1型极化[J]. 第三军医大学学报, 2018,40(1):45-52.

Yun ZHOU, Zhujun YI, Keting QUE, et al. Iron ion polarizes macrophages to M1 subtype through ROS-acetyl-P53[J]. Journal of Third Military Medical University, 2018, 40(1): 45-52.
周赟, 易竹君, 阙克婷, 等. 铁离子通过ROS-乙酰化P53促进巨噬细胞M1型极化[J]. 第三军医大学学报, 2018,40(1):45-52. DOI： 10.16016/j.1000-5404.201709055.

Yun ZHOU, Zhujun YI, Keting QUE, et al. Iron ion polarizes macrophages to M1 subtype through ROS-acetyl-P53[J]. Journal of Third Military Medical University, 2018, 40(1): 45-52. DOI： 10.16016/j.1000-5404.201709055.

摘要

目的

探讨铁离子在促进巨噬细胞向促炎型表型(经典激活型

M1)极化的具体机制。

方法

Western blot、qRT-PCR、流式细胞术(FCM)、组织免疫荧光、ROS探针(DCFH-DA)分别检测巨噬细胞极化指标(IL-1β、TNF-α、IL-10、TGF-β、CD86及CD206等)、p53、乙酰化p53和细胞内活性氧(reactive oxygen species

ROS)水平; 通过还原性谷胱甘肽(reduced glutathione hormone

GSH)和P300/CBP乙酰化转移酶抑制剂(C646)分别处理巨噬细胞后

观察巨噬细胞的极化状态; 通过皮下注射H22肝癌细胞

建立BALB/c裸鼠皮下H22肝癌细胞模型

给予铁剂处理后

观察肿瘤相关巨噬细胞(tumor associated macrophage

TAM)极化状态。

结果

铁剂处理促鼠源性巨噬细胞(RAW 264.7)向M1型极化并高表达乙酰化P53(

0.05);抑制p300/CBP乙酰化转移酶

能够明显抑制p53乙酰化、减弱M1极化效应(

0.05);小鼠皮下瘤模型中

经铁剂处理后

小鼠皮下瘤组织中CD86高表达、CD206低表达

并有更多的ROS产生。

结论

细胞内铁过载促巨噬细胞向M1型极化

其机制可能与ROS产生

提高p300/CBP乙酰化转移酶活性

促进p53乙酰化有关。

Abstract

Objective

To investigate the mechanism of M1 macrophage polarization induced by iron ion.

Methods

Western-blotting

real-time PCR

flow cytometry

immunohistofluorescence assay and reactive oxygen species (ROS) probe (DCFH-DA) were used to verify the effect of iron ion on promoting macrophages to M1 subtype

the expression levels of p53 and acetyl-p53

and the level of ROS production. Polarization indexes (IL-1β

TNF-α

IL-10

TGF-β

CD86 and CD206) were detected following the treatment of reduced glutathione hormone (GSH) or p300/CBP acetyltransferase inhibitor (C646). Ten BALB/c nude mice were divided into 2 groups

iron treatment and control groups. Xenograft model were prepared by subcutaneous injection of H22 cells in BALB/c nude mice to observe the polarization of tumor associated macrophage (TAM) after iron treatment.

Results

Iron polarized macrophages (RAW 264.7 cells) to M1 subtype following the increasing of ROS production and high expression of acetyl-p53. GSH reduced ROS and acetyl-p53 level (

0.05). C646 inhibited the acetylation of p53 and attenuated the polarization of M1 (

0.05). Subcutaneous tumor tissue expressed high level of CD86 and low level of CD206 in high iron treatment group

and a higher level of ROS was observed in the high iron treatment group than control group.

Conclusion

Iron promotes macrophages to M1 subtype

which may be through inducing ROS production

enhancing the activity of p300/CBP acetyltransferase

and then improving acetylation of P53.

关键词

Keywords

references

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