Metformin reduced NLRP3 inflammasome activity in Ox-LDL stimulated macrophages through adenosine monophosphate activated protein kinase and protein phosphatase 2A.

Metformin reduced NLRP3 inflammasome activity in Ox-LDL stimulated macrophages through adenosine monophosphate activated protein kinase and protein phosphatase 2A. Eur J Pharmacol. 2019 Mar 06;: Authors: Zhang L, Lu L, Zhong X, Yue Y, Hong Y, Li Y, Li Y Abstract Metformin has been suggested to have cardiovascular protective effects. Previous researches showed that metformin activates Adenosine Monophosphate Activated Protein Kinase (AMPK) and Protein Phosphatase 2A (PP2A). This research aimed to elucidate whether and how metformin affects NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activity in oxidized low-density lipoprotein (ox-LDL) stimulated macrophages. Macrophages were treated with ox-LDL and metformin in a continuous manner, and NLRP3 inflammasome activation was evaluated by detecting IL-1β and caspase-1 p10 release by ELISA and western blot, respectively. AMPK α1 and α2 gene expression was silenced in macrophages by siRNA transduction. Expression of NLRP3 and pro-IL-1β was monitored by RT-qPCR and western blot. PP2A activity was inhibited by LB-100 treatment. Activation of NF-κB signaling was evaluated by detecting the nuclear accumulation of p65 and phosphorylation of IκBα by western blot. Activation of Tristetraprolin was evaluated by detecting its serine phosphorylation level by immunoprecipitation and western blot. In the results, upregulation of NLRP3 protein expression and NLRP3 inflammasome activat...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research