Atorvastatin suppresses NLRP3 inflammasome activation via TLR4/MyD88/NF-κB signaling in PMA-stimulated THP-1 monocytes

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• 作者：Fanqi Kong ^{676888452@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Bozhi Ye ^{fredye2012@163.com" class="auth_mail" title="E-mail the corresponding author} ; Lu Lin ^{315601953@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Xueli Cai ^{cardiosherry@163.com" class="auth_mail" title="E-mail the corresponding author} ; Weijian Huang ^{weijianhuang69@126.com" class="auth_mail" title="E-mail the corresponding author} ; Zhouqing Huang ; ^{susiehzq@hotmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Atorvastatin ; NLRP3 inflammasome ; TLR4/MyD88/NF-κB ; Atherosclerosis ; Monocytes
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：82
• 期：Complete
• 页码：167-172
• 全文大小：1148 K

文摘

Increasing evidence shows that NLRP3 inflammasome is closely associated with the progression of atherosclerosis. The purpose of the present study was to evaluate the effects of atorvastatin on NLRP3 inflammasome in PMA-stimulated THP-1 cells and explore its underlying mechanism.

Methods

Human monocytic THP-1 cells were pretreated with atorvastatin for 1 h and then induced by PMA for 48 h. Total protein was collected for real-time PCR and Western blot analysis. Cytokine IL-1β release was detected by ELISA assay. And the NF-κB p65 translocation was detected by cellular NF-κB translocation kit.

Results

It was shown that atorvastatin significantly reduced the expression of NLRP3, the cleavage of caspase-1 and IL-1β in PMA-induced THP-1 cells. Moreover, Bay (a NF-κB inhibitor) treatment greatly suppressed the expression of NLRP3, the cleavage of caspase-1 and IL-1β in PMA-induced THP-1 cells, suggesting that the activation of NF-κB pathway takes part in regulating the expression of NLRP3 inflammasome. In addition, atorvastatin markedly inhibited the up-regulation of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and the activation of nuclear factor kappa b (NF-κB) in PMA-stimulated THP-1 cells.

Conclusions

Atorvastatin exerts an anti-inflammatory effect by inhibiting NLRP3 inflammasome through suppressing TLR4/MyD88/NF-κB pathway in PMA-induced THP-1 monocytes.