Silencing triggering receptor expressed on myeloid cells-1 inhibits vascular smooth muscle cell inflammation mediated by trimethylamine N-oxide by regulating the nuclear factor-kappa B signaling pathway

Tan Wenyun; Jing Shuyan; Wang Ruirui; Wang Gang

doi:10.13406/j.cnki.cyxb.003648

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Silencing triggering receptor expressed on myeloid cells-1 inhibits vascular smooth muscle cell inflammation mediated by trimethylamine N-oxide by regulating the nuclear factor-kappa B signaling pathway

Basic research | 更新时间：2025-10-22

- Silencing triggering receptor expressed on myeloid cells-1 inhibits vascular smooth muscle cell inflammation mediated by trimethylamine N-oxide by regulating the nuclear factor-kappa B signaling pathway
- Journal of Chongqing Medical University Vol. 50, Issue 3, Pages: 337-343(2025)
- 作者机构：
  
  1.河北医科大学第一医院急诊科，石家庄 050000
  2.河北医科大学第一医院放射与核医学，石家庄 050000
  3.河北医科大学第一医院心血管内科，石家庄 050000
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.003648
  CLC： R322
- Received：11 June 2024，
  
  Revised：2024-07-23，
  
  Accepted：09 October 2024，
  
  Published：28 March 2025
- 稿件说明：
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谭文云,井淑艳,王蕊蕊,等.沉默TREM-1通过调控NF-κB信号通路抑制氧化三甲胺介导的血管平滑肌细胞炎症[J].重庆医科大学学报,2025,50(3):337-343.

Tan Wenyun,Jing Shuyan,Wang Ruirui,et al.Silencing triggering receptor expressed on myeloid cells-1 inhibits vascular smooth muscle cell inflammation mediated by trimethylamine N-oxide by regulating the nuclear factor-kappa B signaling pathway[J].Journal of Chongqing Medical University,2025,50(3):337-343.
谭文云,井淑艳,王蕊蕊,等.沉默TREM-1通过调控NF-κB信号通路抑制氧化三甲胺介导的血管平滑肌细胞炎症[J].重庆医科大学学报,2025,50(3):337-343. DOI： 10.13406/j.cnki.cyxb.003648.

Tan Wenyun,Jing Shuyan,Wang Ruirui,et al.Silencing triggering receptor expressed on myeloid cells-1 inhibits vascular smooth muscle cell inflammation mediated by trimethylamine N-oxide by regulating the nuclear factor-kappa B signaling pathway[J].Journal of Chongqing Medical University,2025,50(3):337-343. DOI： 10.13406/j.cnki.cyxb.003648.

摘要

目的

探讨髓系细胞触发受体-1（triggering receptors expressed on myeloid cells-1，TREM-1）在氧化三甲胺（trimethylamine oxide，TMAO）介导的大鼠血管平滑肌细胞（vascular smooth muscle cells，VSMCs）炎性反应中的作用及其可能机制。

方法

①采用不同浓度（0、100、300、600、900、1 200、1 500 μmol/L）TMAO处理VSMCs 24 h；②将

TREM-1

基因siRNA干扰质粒（si-

TREM-1

）及其阴性对照干扰质粒（si-NC）转染至VSMCs中，采用600 μmol/L TMAO诱导VSMCs炎性反应，并联合核因子κB（nuclear factor-kappa B，NF-κB）激活剂佛波酯（phorbol myristate acetate，PMA）干预24 h。CCK-8检测细胞增殖活性；ELISA检测细胞上清中白细胞介素（interleukin，IL）-1β、IL-6及肿瘤坏死因子（tumor necrosis factor，TNF）-α水平；定量聚合酶链反应（quantitative polymerase chain reaction，qRT-PCR）检测细胞中TREM-1、环氧化酶-2（cyclooxygenase-2，COX-2）、细胞间黏附分子-1（intercellular adhesion molecule-1，ICAM-1）以及IL-1β、IL-6、TNF-α mRNA表达水平；Western blot检测细胞中TREM-1、COX-2、ICAM-1以及NF-κB p65、p-NF-κB p65（Ser536）蛋白表达水平。

结果

不同浓度TMAO处理对VSMCs细胞增殖活性无明显影响（

=0.375），但可明显上调细胞上清中IL-1β、IL-6、TNF-α水平以及细胞中TREM-1、COX-2、ICAM-1 等mRNA和蛋白表达水平（均

0.01），且呈浓度依赖性。沉默

TREM-1

基因可明显抑制TMAO诱导的VSMCs上清液中IL-1β、IL-6、TNF-α水平的增加，以及细胞中COX-2、ICAM-1、IL-1β、IL-6、TNF-α mRNA和p-NF-κB p65/NF-κB p65蛋白比值的上调（均

0.01）。然而，PMA干预可明显逆转沉默

TREM-1

基因对TMAO诱导VSMCs炎性反应的改善作用。

结论

沉默

TREM-1

基因可抑制TMAO诱导的VSMCs炎性反应，其机制可能与抑制NF-κB通路活化有关。

Abstract

Objective

To investigate the role and possible mechanism of triggering receptor expressed on myeloid cells-1（TREM-1） in the inflammatory response of rat vascular smooth muscle cells（VSMCs） mediated by trimethylamine N-oxide（TMAO）.

Methods

VSMCs were treated with TMAO at different concentrations（0，100，300，600，900，1 200，1 500 μmol/L） for 24 hours. VSMCs were transfected with the siRNA interference plasmid targeting the

TREM-1

gene（si-TREM-1） and its negative control interference plasmid（si-NC），and 600 μmol/L TMAO was used to induce inflammatory response in VSMCs，combined with the intervention with the nuclear factor-kappa B（NF-κB） activator phorbol myristate acetate（PMA） for 24 hours. CCK-8 assay was used to measure cell proliferative activity；ELISA was used to measure the levels of interleukin-1β（IL-1β），interleukin-6（IL-6），and tumor necrosis factor-α（TNF-α） in cell s

upernatant；qRT-PCR was used to measure the mRNA expression levels of TREM-1，cyclooxygenase-2（COX-2），intercellular adhesion molecule-1（ICAM-1），IL-1β，IL-6，and TNF-α in cells，and Western blot was used to measure the protein expression levels of TREM-1，COX-2，ICAM-1，NF-κB p65，and p-NF-κB p65（Ser536） in cells.

Results

Treatment with TMAO at different concentrations had no significant impact on the proliferative activity of VSMCs（

=0.375），but it significantly upregulated the levels of IL-1β，IL-6，and TNF-α in supernatant and the mRNA and protein expression levels of TREM-1，COX-2，and ICAM-1 in cells（all

0.01） in a concentration-dependent manner. Silencing of the

TREM-1

gene significantly inhibited the increases in the levels of IL-1β，IL-6，and TNF-α in the supernatant of VSMCs induced by TMAO，and it also suppressed the upregulation of the mRNA expression levels of COX-2，ICAM-1，IL-1β，IL-6，and TNF-α and the ratio of p-NF-kB p65/NF-kB p65 in VSMCs（all

0.01）. However，PMA intervention significantly reversed the role of silencing the

TREM-1

gene on TMAO-induced inflammatory response in VSMCs.

Conclusion

Silencing of the

TREM-1

gene can inhibit TMAO-induced inflammatory response in VSMCs，possibly by inhibiting the activation of the NF-κB pathway.

关键词

Keywords

references

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