The Effect Of Cholesterol And Its Metabolites Desmosterol And Oxysterol On NLRP3 Inflammasome

Immune system and metabolism system interact with each other and play a vital role in homeostasis.NLRP3 inflammasome was confirmed to play a crucial part in metabolic syndrome,such as atherosclerosis syndrome,type 2 diabetes,gout and so on.Cholesterol and its metabolites sterols and oxysterols are involved in the development of various metabolic diseases.The purpose of this study was to investigate the effects of cholesterol and its metabolites sterols and oxysterols on NLRP3 inflammasome.It was found that low concentrations of cholesterol can inhibit the activation of the NLRP3 inflammasome,sterols and oxysterols can also significantly inhibit the activation of NLRP3 inflammasome,including inhibition of caspase-1 activation and secretion of IL-1β.This process is inhibited by the ASC-Speck and ASC oligomerization formation to affect NLRP3 inflammasome assemble;Further in vivo experiments in animals found that in models of sepsis and peritonitis,both sterol and oxysterol can inhibit the activation of NLRP3 inflammasome.This article reveals the role of the cholesterol metabolic intermediates:sterols and oxysterols,in the process of inflammasome activation,providing the experimental basis for further study of the mechanism.