Thioredoxin-1 attenuates atherosclerosis development through inhibiting NLRP3 inflammasome.

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

Citation

Yu Wang, Ningning Ji, Xinyang Gong, Shimao Ni, Lei Xu, Hui Zhang. Thioredoxin-1 attenuates atherosclerosis development through inhibiting NLRP3 inflammasome. Endocrine. 2020 Oct;70(1):65-70

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PMID: 32607763

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