Cited 4 time in webofscience Cited 4 time in scopus

A translocator protein 18 kDa ligand, Ro5-4864, inhibits ATP-induced NLRP3 inflammasome activation

A translocator protein 18 kDa ligand, Ro5-4864, inhibits ATP-induced NLRP3 inflammasome activation
Lee, JW[Lee, Ji-Won]Kim, LE[Kim, Leah Eunjung]Shim, HJ[Shim, Hyun-Jung]Kim, EK[Kim, Eun-Kyoung]Hwang, WC[Hwang, Won Chan]Min, DS[Min, Do Sik]Yu, SW[Yu, Seong-Woon]
DGIST Authors
Lee, JW[Lee, Ji-Won]; Shim, HJ[Shim, Hyun-Jung]; Kim, EK[Kim, Eun-Kyoung]Yu, SW[Yu, Seong-Woon]
Issue Date
Biochemical and Biophysical Research Communications, 474(3), 587-593
Article Type
Adaptor ProteinAdenosine TriphosphateAnti-Inflammatory AgentCarrier ProteinCells by Body AnatomyCryopyrinDrug MechanismEnzyme ActivationHumanHuman CellInflammasomeInnate ImmunityInterleukin-1 BetaInterleukin-1 Beta Converting EnzymeLigandMacrophageMitochondriaMitochondrial Membrane PotentialMitochondrionMonocyteN Sec Butyl 1 (2 Chlorophenyl) N Methyl 3 IsoquinolinecarboxamideNLRP3Nucleotide Binding Oligomerization Domain Like ReceptorOligomerizationPriority JournalProtein AssemblyRo5-4864Signal TransductionSuperoxideTSPOUnclassified Drug
Ro5-4864 and PK11195, prototypical synthetic ligands of translocator protein 18 kDa (TSPO), have shown anti-inflammatory effects in several models of inflammatory diseases; however, their biochemical mechanisms remain poorly understood. Nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation as a part of the innate immune system, has been implicated in a variety of inflammatory diseases. Here, we demonstrate for the first time that TSPO ligands, especially Ro5-4864, potently suppressed ATP-induced NLRP3 inflammasome activation in THP-1 and BMDM cells. Detailed action mechanism was further investigated in THP-1 cells. Ro5-4864 efficiently attenuated NLRP3 translocation to mitochondria, inflammasome assembly/oligomerization, activation of caspase-1, and subsequent secretion of the mature forms of interleukin-1β and -18. Ro5-4864 also reduced the production of mitochondrial superoxide and preserved the mitochondrial membrane potential in ATP-treated cells, suggesting that Ro5-4864 may act on mitochondria or more upstream targets in NLRP3 inflammasome signaling. We also observed the distinct effects of the TSPO ligands between THP-1 monocytes and macrophages, which suggested different NLRP3 inflammasome signaling depending on cell type. Collectively, our novel findings demonstrate that Ro5-4864 effectively inhibited ATP-induced NLRP3 inflammasome activation through the prevention of mitochondrial perturbation. Our results indicate Ro5-4864 as a promising candidate for the treatment of NLRP3 inflammasome-related diseases. © 2016 Elsevier Inc. All rights reserved.
Elsevier B.V.
Related Researcher
  • Author Yu, Seong Woon Laboratory of Neuronal Cell Death
  • Research Interests Molecular mechanisms of neuronal cell death and neurodegeneration
There are no files associated with this item.
Department of Brain and Cognitive SciencesLaboratory of Neuronal Cell Death1. Journal Articles

qrcode mendeley

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.