Curcumin Represses NLRP3 Inflammasome Activation via TLR4/MyD88/NF-κB and P2X7R Signaling in PMA-Induced Macrophages.
Curcumin Represses NLRP3 Inflammasome Activation via TLR4/MyD88/NF-κB and P2X7R Signaling in PMA-Induced Macrophages.
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姜黄素通过 PMA 诱导的巨噬细胞中的 TLR4/MyD88/NF-κB 和 P2X7R 信号传导抑制 NLRP3 炎症小体激活
DOI：
10.3389/fphar.2016.00369
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发表时间：
2016
影响因子：
5.6
通讯作者：
Huang Z
中科院分区：
文献类型：
--
作者：
Kong F;Ye B;Cao J;Cai X;Lin L;Huang S;Huang W;Huang Z
目的：在nod样受体（NLR）家族中，pyrin domain containing 3 （NLRP3）炎性小体与动脉粥样硬化的进展密切相关。本研究旨在探讨姜黄素对PMA诱导巨噬细胞NLRP3炎性体的影响，并探讨其机制。方法：姜黄素预处理人THP-1单核细胞1 h， PMA诱导48 h，收集总蛋白进行Western blot分析。分别采用ELISA法和细胞NF-κB易位试剂盒检测细胞因子白细胞介素(IL)-1β释放和核因子κB (NF-κB) p65易位。结果：姜黄素可显著降低pma诱导的巨噬细胞NLRP3的表达，抑制caspase-1和IL-1β的分泌。此外，Bay（一种NF-κB抑制剂）处理显著抑制了pma诱导的THP-1细胞中NLRP3炎症小体的表达。姜黄素还能显著抑制pma诱导的巨噬细胞toll样受体4 （TLR4）、髓样分化因子88 （MyD88）、i -κB -α磷酸化水平和NF-κB活化的上调。此外，给予嘌呤能2X7受体（P2X7R） siRNA，可显著降低pma诱导的巨噬细胞中NLRP3炎性体的表达。此外，姜黄素逆转pma刺激的P2X7R激活，从而进一步降低NLRP3的表达和caspase-1和IL-1β的分泌。siRNA沉默P2X7R也抑制了pma诱导的巨噬细胞中NF-κB通路的激活，但P2X7R沉默细胞没有显著降低TLR4和MyD88的表达。结论：姜黄素通过抑制pma诱导巨噬细胞的TLR4/MyD88/NF-κB和P2X7R通路抑制NLRP3炎性体。
Aims: In the NOD-like receptor (NLR) family, the pyrin domain containing 3 (NLRP3) inflammasome is closely related to the progression of atherosclerosis. This study aimed to assess the effects of curcumin on NLRP3 inflammasome in phorbol 12-myristate 13-acetate (PMA)-induced macrophages and explore its underlying mechanism. Methods: Human monocytic THP-1 cells were pretreated with curcumin for 1 h and subsequently induced with PMA for 48 h. Total protein was collected for Western blot analysis. Cytokine interleukin (IL)-1β release and nuclear factor kappa B (NF-κB) p65 translocation were detected by ELISA assay and cellular NF-κB translocation kit, respectively. Results: Curcumin significantly reduced the expression of NLRP3 and cleavage of caspase-1 and IL-1β secretion in PMA-induced macrophages. Moreover, Bay (a NF-κB inhibitor) treatment considerably suppressed the expression of NLRP3 inflammasome in PMA-induced THP-1 cells. Curcumin also markedly inhibited the upregulation of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), phosphorylation level of IκB-α, and activation of NF-κB in PMA-induced macrophages. In addition, purinergic 2X7 receptor (P2X7R) siRNA was administered, and it significantly decreased NLRP3 inflammasome expression in PMA-induced macrophages. Furthermore, curcumin reversed PMA-stimulated P2X7R activation, which further reduced the expression of NLRP3 and cleavage of caspase-1 and IL-1β secretion. Silencing of P2X7R using siRNA also suppressed the activation of NF-κB pathway in PMA-induced macrophages, but P2X7R-silenced cells did not significantly decrease the expression of TLR4 and MyD88. Conclusion: Curcumin inhibited NLRP3 inflammasome through suppressing TLR4/MyD88/NF-κB and P2X7R pathways in PMA-induced macrophages.
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