Thioredoxin-1 attenuates atherosclerosis development through inhibiting NLRP3 inflammasome

Abstract

Backgrounds

The thioredoxin-1 has atheroprotective effects via regulating oxidative stress and inflammation. In addition, the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome also contributes to atherosclerosis development. However, whether the thioredoxin-1 suppresses atherosclerosis development by modulating the NLRP3 inflammasome remains unclear.

Methods

The regulation of NLRP3 inflammasome by thioredoxin-1 was determined in vitro on macrophage cells after ox-LDL (oxidized low-density lipoprotein) stimulation. The IL-1β and caspase-1 p10 secretion were assessed by ELISA and western blot. Finally, the thioredoxin-1/NLRP3 inflammasome pathway was confirmed in apolipoprotein E-deficient mice.

Results

Thioredoxin-1 suppressed the expression of NLRP3, the secretion of IL-1β and caspase-1 p10 in vitro. And ROS stimulation activated the NLRP3 inflammasome which was inhibited by thioredoxin-1. In the mouse model of atherosclerosis, thioredoxin-1 delivered by lentivirus vector inhibited atherosclerosis development. And the atheroprotective effects of thioredoxin-1 were attenuated by ROS stimulation. Furthermore, the regulation of NLRP3 inflammasome by thioredoxin-1 was also confirmed in vivo.

Conclusions

We demonstrated here that the thioredoxin-1 had atheroprotective functions through thioredoxin-1/NLRP3 inflammasome pathway.

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Data availability

All data have been presented in the figures. And other related information are available under request to the corresponding author.

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Funding

This study was funded by Science Program of Yiwu, Zhejiang (Grant Number NO. 18-3-90).

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Correspondence to Hui Zhang.

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Wang, Y., Ji, N., Gong, X. et al. Thioredoxin-1 attenuates atherosclerosis development through inhibiting NLRP3 inflammasome. Endocrine (2020). https://doi.org/10.1007/s12020-020-02389-z

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Keywords

  • Thioredoxin-1
  • Trx-1
  • Atherosclerosis
  • NLRP3