Peroxisome proliferators-activated receptor-γ inhibits inflammatory response by upregulating miR-16 in sepsis

Xiaoping SUN; Yangjia DENG; Jiajun LI; Haibo GUI; Qian WU; Lei DU; Jin ZHANG

doi:10.16016/j.1000-5404.201708075

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Peroxisome proliferators-activated receptor-γ inhibits inflammatory response by upregulating miR-16 in sepsis

Basic Medicine | 更新时间：2026-01-09

- Peroxisome proliferators-activated receptor-γ inhibits inflammatory response by upregulating miR-16 in sepsis
- Journal of Third Military Medical University Vol. 40, Issue 2, Pages: 141-148(2018)
- 作者机构：
  
  1.400011 重庆, 重庆市中医院(道门口院部)重症医学科
  2.400016 重庆，重庆医科大学附属第一医院感染科
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.201708075
  CLC： R364.5;R392.13;R63
- Received：14 August 2017，
  
  Revised：2017-11-06，
  
  Published：30 January 2018
- 稿件说明：
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Xiaoping SUN, Yangjia DENG, Jiajun LI, et al. Peroxisome proliferators-activated receptor-γ inhibits inflammatory response by upregulating miR-16 in sepsis[J]. Journal of Third Military Medical University, 2018, 40(2): 141-148.
DOI：

Xiaoping SUN, Yangjia DENG, Jiajun LI, et al. Peroxisome proliferators-activated receptor-γ inhibits inflammatory response by upregulating miR-16 in sepsis[J]. Journal of Third Military Medical University, 2018, 40(2): 141-148. DOI： 10.16016/j.1000-5404.201708075.

摘要

目的

探讨PPARγ上调miR-16的机制及其抑制脓毒症炎症反应的作用。

方法

经Real time RT-PCR检测脓毒症患者和健康者的外周血单核细胞PPARγ和miR-16的表达，分析其相关性; 分别用PPARγ激动剂RGZ、PPARγ siRNA或miR-16抑制剂(antagomir-16)处理THP-1和RAW246.7，经real time RT-PCR和Western blot检测miR-16及其靶基因IKKα的表达; 细胞转染含miR-16启动子的报告基因质粒，经PPARγ激动剂RGZ或拮抗剂GW9662处理后，检测细胞报告基因活性; 细胞经PPARγ激动剂RGZ处理，再经LPS处理，ELISA检测炎症因子TNFα和IL-6的表达; LPS诱导的脓毒症小鼠经PPARγ激动剂RGZ，或经antagomir-16预处理后，再经PPARγ激动剂RGZ处理小鼠，real time RT-PCR检测小鼠外周血单核细胞中miR-16的表达，ELISA检测血清炎症因子TNFα和IL-6的表达。

结果

脓毒症患者外周血单核细胞中PPARγ与miR-16的表达均降低且二者的表达呈显著负相关(

0.05);PPARγ通过促进miR-16的启动子活性上调miR-16的表达，进而抑制miR-16靶分子IKKα的表达(

0.05); PPARγ上调miR-16后显著抑制炎症细胞产生TNFα和IL-6(

0.05);PPARγ上调miR-16抑制脓毒症小鼠血清TNFα和IL-6的表达(

0.05)。

结论

激动剂活化的PPARγ上调miR-16进而抑制细胞炎症因子表达及脓毒症小鼠炎症反应。

Abstract

Objective

To explore the mechanism by which peroxisome proliferators-activated receptor-γ (PPARγ) upregulates miR-16 and inhibits inflammatory response in sepsis.

Methods

Real-time PCR was used to investigate the expression of PPARγ and miR-16 in peripheral blood monocytes of patients with sepsis and healthy subjects

and the correlation between PPARγ and miR-16 was analyzed. THP-1 and RAW246.7 cells were treated with the PPARγ agonist RGZ

PPARγ siRNA or a ir-16 inhibitor (antagomir-16)

and the changes in the expressions of miR-16 and its target gene IKKα were detected using real-time PCR and Western blotting. The cells were transfected with luciferase reporter gene plasmid containing the miR-16 promoter region followed by treatment with RGZ or the PPARγ antagonist GW9662

and luciferase reporter assay was performed to detect the changes in the reporter gene activity. In cells treated with RGZ followed then by LPS

the expression levels of the inflammatory factors tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) were detected using ELISA. In a mouse model of LPS-induced sepsis

following treatment with RGZ with or without antagomir-16 pretreatment

the expression of miR-16 in peripheral blood monocytes was detected with real-time PCR

and the expression of TNFα and IL-6 were determined using ELISA.

Results

The expressions of PPARγ and miR-16 in peripheral blood monocytes were significantly reduced in patients with sepsis (

0.05). In THP-1 and RAW246.7 cells

the activation of PPARγ obviously increased the expression of miR-16 by enhancing the transcriptional activity of miR16 promoter and consequently inhibited the expression of IKKα

the target gene of miR-16 (

0.05). PPARγ inhibited production of TNFα and IL-6 in the inflammatory cells by increasing the expression of miR-16 (

0.05). Treatment with PPARγ significantly decreased the serum levels of TNFα and IL-6 in mouse models of LPS-induced sepsis (

0.05).

Conclusion

Activation of PPARγ inhibits the expression of inflammatory cytokines in inflammatory cells and suppresses inflammatory response in septic mice by upregulating miR-16.

关键词

Keywords

references

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