阿托伐他汀通过下调NLRP1炎性体表达抑制IL-1β和IL-18的释放

Atorvastatin inhibits IL-1β and IL-18 releases via lowering the expression of NLRP1 inflammasome

目的:探讨核苷酸结合寡聚化结构域样受体蛋白1(NLRP1)炎性体在阿托伐他汀抑制THP-1巨噬细胞白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)分泌中的作用。方法:用10μg/L脂多糖诱导THP-1巨噬细胞分泌IL-1β和IL-18,以不同浓度阿托伐他汀(1、10和20μmol/L)孵育细胞24 h,或以10μmol/L阿托伐他汀处理细胞不同时间(12、24和48 h),或转染NLRP1 siRNA以沉默细胞内NLRP1的表达。采用RT-PCR检测细胞内NLRP1炎性体mRNA的表达,Western blot检测细胞内NLRP1炎性体蛋白的表达,ELISA检测细胞上清液中IL-1β和IL-18的含量。结果:阿托伐他汀可抑制THP-1巨噬细胞NLRP1炎性体mRNA和蛋白的表达,且这种效应呈浓度和时间依赖性。转染NLRP1 siRNA后,THP-1巨噬细胞NLRP1的蛋白表达明显下降,且阿托伐他汀对IL-1β和IL-18分泌的抑制作用明显增强。结论:阿托伐他汀通过抑制NLRP1炎性体表达减少巨噬细胞IL-1β和IL-18的释放,发挥抗炎作用,进而延缓动脉粥样硬化进展。

AIM： To explore the role of nucleotide-binding oligomerization domain-like receptor protein 1（ NLRP1） inflammasome in atorvastatin-induced reduction of interleukin-1β（ IL-1β） and interleukin-18（ IL-18） releases from the THP-1 macrophages. METHODS： Lipopolysaccharide（ LPS,10 μg / L） was used to trigger the secretion of IL-1β and IL-18 in the THP-1 macrophages. The cells were incubated with different concentrations of atorvastatin（ 1,10 and 20μmol /L） for 24 h,or treated with 10 μmol /L atorvastatin for different time（ 12 h,24 h and 48 h）. NLRP1 siRNA was transfected into the THP-1 cells. The mRNA expression of NLRP1 inflammasome was detected by RT-PCR. The protein expression of NLRP1 inflammasome was determined by Western blot. The secretion of proinflammatory cytokines IL-1β and IL-18 was quantified by ELISA. RESULTS： Atorvastatin inhibited the mRNA and protein expression of NLRP1 inflammasome in the THP-1 macrophages in a dose- and time-dependent manner. Transfection of NLRP1 siRNA significantly decreased the protein expression of NLRP1 and promoted the suppressive effect of atorvastatin on IL-1β and IL-18 secretion in the THP-1 macrophages. CONCLUSION： Atorvastatin inhibits the production of IL-1β and IL-18 in the macrophages through decreasing NLRP1 inflammasome expression,possibly contributing to the anti-inflammatory effect of atorvastatin on atherosclerosis.