The Role Of NLRP1 Inflammasome In The Suppressive Effect Of Atorvastatin On THP-1 Macrophage Pro-inflammatory Cytokines Secretion

Objectives NLRP1 inflammasome is a intracellular multi-protein complex which consists of NLRP1, Caspase-1, and ASC. Once activated, NLRP1 inflammasome is able to promote the secretion of pro-inflammatory cytokines such as IL-1β and IL-18, thereby playing an important role in atherosclerosis and other inflammatory diseases. This study aims to observe the effect of atorvastatin on IL-1β and IL-18 production in THP-1 macrophages as well as the regulatory role of NLRP1 inflammasome in this process, and to explore the anti-inflammatory effect of atorvastatin, providing new evidence for non-lipid modulating effect of this drug and its widely use in atherosclerosis.Methods THP-1 cells were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum. After 3-4 d, THP-1 cells were seeded in six-well plates with PMA(100 nmol/L) for 24 h to be differentiated into macrophages. The medium was then replaced with serum-free medium containing LPS(10 ng/ml) for 24 h so as to let cells transform into foam cells for the subsequent experiments. The cells were then treated with 1, 10, 20 μM atorvastatin for 24 h, or treated with 10μM atorvastatin for 12, 24, 48 h, or transfected with NLRP1 si RNA. Levels of IL-1β and IL-18, m RNA and protein expression of NLRP1 inflammasome(NLRP1, Caspase-1, and ASC) were quantified via ELISA, RT-PCR, and Western blot, respectively.Results Compared with the control, the expression of NLRP1 inflammasome(NLRP1, Caspase-1, and ASC) m RNA and protein, as well as the levels of IL-1β and IL-18 were significantly increased in THP-1 cells treated with LPS. However, atorvastatin incubation dose-dependently and time-dependently inhibited the expression of these induced by LPS; In addtion, we employed si RNA to knockdown NLRP1 in THP-1 cells, and discovered that these NLRP1 silencing cells resulted in significantly reduced levels of IL-1β and IL-18.Conclusion Atorvastatin decreases IL-1β and IL-18 secretion via inhibition of NLRP1 inflammasome in THP-1 macrophages, possibly contributing to its anti-inflammatory effect and anti-atherogenic actions.