NLRP3 inflammasome: a novel link between lipoproteins and atherosclerosis.
BACKGROUND
Pattern recognition receptor-mediated signaling pathways have recently been elucidated to bridge the innate immune system and atherosclerosis. NLRP3 is a member of the NLR family. Upon activation, it initiates IL-1β and IL-18 processing, a key step in the inflammatory process of atherosclerosis.


METHODS
We used three different types of lipoproteins, ox-LDL, ox-HDL, and HDL, in Thp-1 at the concentration of 50 mg/l, 100 mg/l, and 150 mg/l respectively. Using real-time polymerase chain reaction and western blot, ELISA detected the expression of NLRP3 and downstream cytokines. NLRP3 siRNA was constructed to down-regulate expression of the NLRP3 gene via the RNA interference technique. 150 mg/l of ox-LDL, ox-HDL and HDL was added to the Thp-1 cell line respectively. We observed the changes in the expression of caspase-1, IL-1β and IL-18 when the NLRP3 gene was down-regulated.


RESULTS
Ox-LDL and ox-HDL addition not only increases the expression of NLRP3, but also activates the NLRP3 downstream cytokines and caspase-1 and induces IL-1β and IL-18 secretion. Moreover, the effects of activation and induction are shown to have a dose-dependent manner. Expression of NLRP3 and its downstream inflammatory cytokines is reduced in the presence of HDL (p< 0.05). Furthermore, our data demonstrated that NLRP3 siRNA downregulates NLRP3 expression in mononuclear cells, thus leading to a dramatic reduction in the expression of caspase-1, IL-1β and IL-18 (p< 0.05).


CONCLUSIONS
The data suggest that activation of the NLRP3 inflammasome is a critical step in caspase-1 activation and IL-1β and IL-18 secretion. Interference with the NLRP3 inflammasome can significantly inhibit the generation of cytokines, thus impeding the pathogenesis of inflammation.
Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Wang Li
WL
Li
Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Li Gui
LG
Hua
Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Peng
P
Qu
Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Wang Hong
WH
Yan
Department of Emergency, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Cui
C
Ming
Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Yuan Da
YD
Jun
Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Lou Da
LD
Yuan
Department of Cardiology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Niu
N
Nan
NLRP3; atherosclerosis; inflammasome; lipoprotein; monocytes
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