MicroRNA-132 Negatively Regulates Palmitate-Induced NLRP3 Inflammasome Activation through FOXO3 Down-Regulation in THP-1 Cells. 2017

Hye-Eun Byeon, and Ja Young Jeon, and Hae Jin Kim, and Dae Jung Kim, and Kwan-Woo Lee, and Yup Kang, and Seung Jin Han
Institute of Medical Science, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Korea. 110236@aumc.ac.kr.

Saturated fatty acids were proposed to activate the NLRP3 inflammasome, a molecular platform that mediates the processing of interleukin (IL)-1β 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-1β; caspase-1 activity; and IL-1β 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-1β, 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.

UI MeSH Term Description Entries
D010168 Palmitates Salts and esters of the 16-carbon saturated monocarboxylic acid--palmitic acid. Hexadecanoates,Palmitate
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071199 NLR Family, Pyrin Domain-Containing 3 Protein An NLR protein that contains an N-terminal PYRIN DOMAIN and ATP-binding site and 9 C-terminal LEUCINE-rich repeats; it is expressed primarily by MACROPHAGES. It is a core component of the INFLAMMASOME and directs its assembly in response to pathogen infection and damage-associated stimuli. Mutations in the NLRP3 gene are associated with FAMILIAL COLD AUTOINFLAMMATORY SYNDROME. Cold Autoinflammatory Syndrome 1 Protein,NACHT, LRR and PYD Domains-Containing Protein 3,NLRP3 Protein,NACHT, LRR and PYD Domains Containing Protein 3,NLR Family, Pyrin Domain Containing 3 Protein
D000071316 Forkhead Box Protein O3 A forkhead box transcription factor and transcriptional activator which triggers type 1 programmed cell death (APOPTOSIS) in the absence of APOPTOSIS INHIBITING PROTEINS, including neuronal cell death induced by OXIDATIVE STRESS. It recognizes and binds to the DNA sequence 5'-(AG)TAAA(TC)A-3' and also functions in post-transcriptional regulation of the c-MYC PROTO-ONCOGENE. FOXO3 Protein,Forkhead in Rhabdomyosarcoma-Like 1 Protein,Forkhead in Rhabdomyosarcoma Like 1 Protein,Protein, FOXO3
D000074084 THP-1 Cells A human leukemia monocytic cell line derived from a patient with LEUKEMIA, MONOCYTIC, ACUTE. It is used as a model to study the function of MONOCYTES and MACROPHAGES, their signaling pathways, nutrient and drug transport. THP-1 Cell Line,Cell Line, THP-1,Cell Lines, THP-1,Cell, THP-1,Cells, THP-1,THP 1 Cell Line,THP 1 Cells,THP-1 Cell,THP-1 Cell Lines
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D053583 Interleukin-1beta An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane. IL-1 beta,Catabolin,Interleukin-1 beta,Interleukin 1 beta,Interleukin 1beta
D058847 Inflammasomes Multiprotein complexes that mediate the activation of CASPASE-1. Dysregulation of inflammasomes has also been linked to a number of autoinflammatory and autoimmune disorders. Inflammasome,Pyroptosome,Pyroptosomes
D020170 Caspase 1 A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE. ICE Protease,IL-1 beta-Converting Enzyme,Interleukin-1beta Converting Enzyme,CASP1 Caspase,IL-1 beta Convertase,IL1BC Enzyme,Interleukin-1 Converting Enzyme,Pro-Caspase-1,Procaspase-1,Caspase, CASP1,Convertase, IL-1 beta,Converting Enzyme, Interleukin-1,Converting Enzyme, Interleukin-1beta,IL 1 beta Convertase,IL 1 beta Converting Enzyme,Interleukin 1 Converting Enzyme,Interleukin 1beta Converting Enzyme,Pro Caspase 1,Procaspase 1,beta Convertase, IL-1,beta-Converting Enzyme, IL-1
D020382 Interleukin-18 A cytokine which resembles IL-1 structurally and IL-12 functionally. It enhances the cytotoxic activity of NK CELLS and CYTOTOXIC T-LYMPHOCYTES, and appears to play a role both as neuroimmunomodulator and in the induction of mucosal immunity. IFN-gamma-Inducing Factor,IL-18,Interferon-gamma-Inducing Factor,IFN-gamma Inducing Factor,IL18,Interferon-gamma Inducing Factor,IFN gamma Inducing Factor,Inducing Factor, IFN-gamma,Inducing Factor, Interferon-gamma,Interferon gamma Inducing Factor,Interleukin 18

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