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MicroRNA-132 Negatively Regulates Palmitate-Induced NLRP3 Inflammasome Activation through FOXO3 Down-Regulation in THP-1 Cells

Byeon, HE; Jeon, JY; Kim, HJ; Kim, DJ; Lee, KW; Kang, Y; Han, SJ
Nutrients, 9(12):E1370-E1370, 2017
Journal Title
Saturated fatty acids were proposed to activate the NLRP3 inflammasome, a molecular platform that mediates the processing of interleukin (IL)-1beta and IL-18. However, the mechanisms underlying the miRNA-mediated regulation of palmitate (PA)-induced inflammasome activation are unclear. We examined the role of miR-132 in PA-induced NLRP3 inflammasome activation in THP-1 cells. To understand the regulatory role of miR-132 in inflammasome activation, we either overexpressed or suppressed miR-132 in THP-1 cells that expressed the NLRP3 inflammasome in response to stimulation by PA. We analyzed the mRNA and protein levels of NLRP3, caspase-1 p10, IL-18, and IL-1beta: caspase-1 activity: and IL-1beta secretion. The presence of PA activated the NLRP3 inflammasome and increased miR-132 expression. Overexpression of miR-132 reduced caspase-1 p10, IL-18, and IL-1beta, while the suppression of miR-132 enhanced inflammasome activation. In addition, miR-132 regulated the mRNA and protein expression of FOXO3, which is a potential target of miR-132 in these cells. FOXO3 suppression by small interfering RNA decreased NLRP3 inflammasome activity stimulated by PA. Knockdown of FOXO3 attenuated NLRP3 inflammasome activation by the miR-132 inhibitor. Based on these findings, we conclude that miR-132 negatively regulates PA-induced NLRP3 inflammasome activation through FOXO3 down-regulation in THP-1 cells.
MeSH terms
Caspase 1/geneticsCaspase 1/metabolismDown-RegulationForkhead Box Protein O3/geneticsForkhead Box Protein O3/metabolism*HumansInflammasomes/geneticsInflammasomes/metabolism*Interleukin-18/geneticsInterleukin-18/metabolismInterleukin-1beta/geneticsInterleukin-1beta/metabolismMicroRNAs/geneticsMicroRNAs/metabolism*NLR Family, Pyrin Domain-Containing 3 Protein/geneticsNLR Family, Pyrin Domain-Containing 3 Protein/metabolism*Palmitates/toxicity*THP-1 Cells
Appears in Collections:
Journal Papers > Research Organization > Institute for Medical Sciences
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
변, 혜은전, 자영김, 혜진김, 대중이, 관우강, 엽한, 승진
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