Oxidized low-density lipoprotein induces secretion of interleukin-1β by macrophages via reactive oxygen species-dependent NLRP3 inflammasome activation.
Oxidized low-density lipoprotein (ox-LDL) is a critical mediator of atherogenesis. Macrophage uptake of ox-LDL and their subsequent development into foam cells is the principal event in atherosclerosis. Interleukin-1β (IL-1β), a prototypic multifunctional cytokine involved in inflammation, has an important effect on the pathogenesis and progression of atherosclerosis. Here we show that the phagocytosis of ox-LDL can induce human macrophages to secrete IL-1β by activating the NLRP3 inflammasome, and we further show that the activation of the NLRP3 inflammasome is dependent on the generation of reactive oxygen species and is related to the cathepsin B pathway. Furthermore, ox-LDL can upregulate the expression of the pro-IL-1β protein, thus priming IL-1β secretion. Therefore, our results suggest that the role of ox-LDL in atherosclerosis-related inflammation may involve the activation of the NLRP3 inflammasome.
Division of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, PR China.
Yugang
Y
Jiang
Mian
M
Wang
Kai
K
Huang
Zhihui
Z
Zhang
Nan
N
Shao
Yuanqi
Y
Zhang
Wenjian
W
Wang
Shenming
S
Wang
D050197:Atherosclerosis / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D058847:Inflammasomes / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology*; D008077:Lipoproteins, LDL / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010587:Phagocytosis; D017382:Reactive Oxygen Species / Q000378:metabolism*
D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D008077:Lipoproteins, LDL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; C533912:CTSB protein, human; D002401:Cathepsin B; D020170:Caspase 1