Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Lee, Ji-Won | - |
dc.contributor.author | Kim, Leah Eunjung | - |
dc.contributor.author | Shim, Hyun-Jung | - |
dc.contributor.author | Kim, Eun-Kyoung | - |
dc.contributor.author | Hwang, Won Chan | - |
dc.contributor.author | Min, Do Sik | - |
dc.contributor.author | Yu, Seong-Woon | - |
dc.date.available | 2017-07-05T08:38:43Z | - |
dc.date.created | 2017-04-10 | - |
dc.date.issued | 2016-06-03 | - |
dc.identifier.issn | 0006-291X | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/2263 | - |
dc.description.abstract | 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. | - |
dc.publisher | Elsevier B.V. | - |
dc.title | A translocator protein 18 kDa ligand, Ro5-4864, inhibits ATP-induced NLRP3 inflammasome activation | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.bbrc.2016.04.080 | - |
dc.identifier.scopusid | 2-s2.0-84968820370 | - |
dc.identifier.bibliographicCitation | Biochemical and Biophysical Research Communications, v.474, no.3, pp.587 - 593 | - |
dc.subject.keywordAuthor | TSPO | - |
dc.subject.keywordAuthor | Ro5-4864 | - |
dc.subject.keywordAuthor | NLRP3 | - |
dc.subject.keywordAuthor | Inflammasome | - |
dc.subject.keywordAuthor | Mitochondria | - |
dc.subject.keywordPlus | Adaptor Protein | - |
dc.subject.keywordPlus | Adenosine Triphosphate | - |
dc.subject.keywordPlus | AntIInflammatory Agent | - |
dc.subject.keywordPlus | Article | - |
dc.subject.keywordPlus | Carrier Protein | - |
dc.subject.keywordPlus | Cells by Body Anatomy | - |
dc.subject.keywordPlus | Cryopyrin | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | Drug Mechanism | - |
dc.subject.keywordPlus | Enzyme Activation | - |
dc.subject.keywordPlus | Human | - |
dc.subject.keywordPlus | Human Cell | - |
dc.subject.keywordPlus | Inflammasome | - |
dc.subject.keywordPlus | INNATE IMMUNITY | - |
dc.subject.keywordPlus | Interleukin 1Beta | - |
dc.subject.keywordPlus | Interleukin 1Beta Converting Enzyme | - |
dc.subject.keywordPlus | Ligand | - |
dc.subject.keywordPlus | Macrophage | - |
dc.subject.keywordPlus | Mitochondria | - |
dc.subject.keywordPlus | Mitochondrial Membrane Potential | - |
dc.subject.keywordPlus | Mitochondrion | - |
dc.subject.keywordPlus | Monocyte | - |
dc.subject.keywordPlus | MOUSE MODEL | - |
dc.subject.keywordPlus | N Sec Butyl 1 (2 Chlorophenyl) N Methyl 3 Isoquinolinecarboxamide | - |
dc.subject.keywordPlus | NLRP3 | - |
dc.subject.keywordPlus | Nucleotide Binding Oligomerization Domain Like Receptor | - |
dc.subject.keywordPlus | Oligomerization | - |
dc.subject.keywordPlus | PERIPHERAL BENZODIAZEPINE-RECEPTOR | - |
dc.subject.keywordPlus | Priority Journal | - |
dc.subject.keywordPlus | Protein Assembly | - |
dc.subject.keywordPlus | Ro5-4864 | - |
dc.subject.keywordPlus | Signal Transduction | - |
dc.subject.keywordPlus | Superoxide | - |
dc.subject.keywordPlus | TSPO | - |
dc.subject.keywordPlus | Unclassified Drug | - |
dc.citation.endPage | 593 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 587 | - |
dc.citation.title | Biochemical and Biophysical Research Communications | - |
dc.citation.volume | 474 | - |
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