SREBP1 在阿托伐他汀抑制NLRP1 炎性体表达中的作用

目的:探讨固醇调节元件结合蛋白1(SREBP1)在阿托伐他汀抑制核苷酸结合寡聚化结构域样受体蛋白1(NLRP1)炎性体表达中的作用。方法:160 nmol/ L 佛波酯孵育THP- 1 细胞12 h,使其分化为巨噬细胞,更换无血清培养基,加入脂多糖和(或)阿托伐他汀进行处理。Real-time PCR 检测细胞中NLRP1、SREBP1 mRNA 的表达;Western blot 检测细胞中NLRP1、SREBP1 蛋白的表达;检测SREBP1 siRNA 预处理细胞后对阿托伐他汀抑制NLRP1 表达的影响。结果:阿托伐他汀能抑制THP-1 巨噬细胞NLRP1 和SREBP1 的mRNA 和蛋白的表达;单独使用SREBP1 siRNA 处理细胞可有效抑制NLRP1 的表达,且与单独使用阿托伐他汀无明显差异;同时使用SREBP1 siRNA 和阿托伐他汀处理细胞比单独使用一种对NLRP1 的抑制作用更为显著。结论:阿托伐他汀可能通过SREBP1 途径抑制NLRP1 的表达,进而发挥抗炎效应。

Role of SREBP1 in atorvastatin-induced reduction of NLRP1 inflammasome expression

Objective:To investigate the role of sterol regulatory element binding protein-1 (SREBP1) in atorvastatin-induced reduction of nucleotide-binding oligomerization domain-like receptor protein 1 (NLRP1) inflammasome expression.Methods:THP-1 cells were treated with phorbol 12-myristate 13-acetate (160 nmol/ L) for 12 h to be differentiated into macrophages.The medium was then replaced with serum-free medium containing lipopolysaccharide and (or) atorvastatin.The mRNA expression of NLRP1 and SREBP1 were detected by Real-time PCR.The protein expression of NLRP1 and SREBP1 were determined by Western blot.Furthermore,we observed the effect of SREBP1 siRNA on atorvastatin-induced reduction of NLRP1 expression.Results: Atorvastatin inhibited the mRNA and protein expression of NLRP1 and SREBP1 in the THP-1 macrophages.SREBP1 siRNA showed no significant difference on lowering NLRP1 expression when compared with atorvastatin.Treating cells with SREBP1 siRNA and atorvastatin at the same time resulted in more obvious reduction of NLRP1 expression than single use of SREBP1 siRNA or atorvastatin. Conclusion:Atorvastatin might exert anti-inflammatory effect by repressing NLRP1 expression through the SREBP1 pathway.