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Non-transcriptional regulation of NLRP3 inflammasome signaling by IL-4

DC Field Value Language
dc.contributor.author유제욱-
dc.contributor.author황인화-
dc.date.accessioned2016-02-04T11:29:45Z-
dc.date.available2016-02-04T11:29:45Z-
dc.date.issued2015-
dc.identifier.issn0818-9641-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/140552-
dc.description.abstractTh2 cytokine IL-4 has been previously shown to suppress the production of proinflammatory cytokines in monocytes. However, the underlying molecular mechanism by which IL-4 signaling antagonizes proinflammatory responses is poorly characterized. In particular, whether IL-4 can modulate inflammasome signaling remains unknown. Here, we provide evidence that IL-4 suppresses NLRP3-dependent caspase-1 activation and the subsequent IL-1β secretion but does not inhibit absent in melanoma 2 (AIM2)- or NLRC4 (NOD-like receptor family, CARD domain-containing 4)-dependent caspase-1 activation in THP-1 and mouse bone marrow-derived macrophages. Upon lipopolysaccharide (LPS) or LPS/ATP stimulation, IL-4 markedly inhibited the assembly of NLRP3 inflammasome, including NLRP3-dependent ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) oligomerization, NLRP3-ASC interaction and NLRP3 speck-like oligomeric structure formation. The negative regulation of NLRP3 inflammasome by IL-4 was not due to the impaired mRNA or protein production of NLRP3 and proinflammatory cytokines. Supporting this observation, IL-4 attenuated NLRP3 inflammasome activation even in reconstituted NLRP3-expressing macrophages in which NLRP3 expression is not transcriptionally regulated by TLR-NF-κB signaling. Furthermore, the IL-4-mediated suppression of NLRP3 inflammasome was independent of STAT6-dependent transcription and mitochondrial reactive oxygen species (ROS). Instead, IL-4 inhibited subcellular redistribution of NLRP3 into mitochondria and microtubule polymerization upon NLRP3-activating stimulation. Our results collectively suggest that IL-4 could suppress NLRP3 inflammasome activation in a transcription-independent manner, thus providing an endogenous regulatory machinery to prevent excessive inflammasome activation.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfIMMUNOLOGY AND CELL BIOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHCarrier Proteins/metabolism*-
dc.subject.MESHCaspase 1/metabolism-
dc.subject.MESHCytokines/genetics-
dc.subject.MESHCytokines/metabolism-
dc.subject.MESHEnzyme Activation/drug effects-
dc.subject.MESHHumans-
dc.subject.MESHInflammasomes/metabolism*-
dc.subject.MESHInflammation Mediators/metabolism-
dc.subject.MESHInterleukin-4/metabolism*-
dc.subject.MESHInterleukin-4/pharmacology-
dc.subject.MESHIntracellular Space-
dc.subject.MESHLipopolysaccharides/immunology-
dc.subject.MESHLipopolysaccharides/pharmacology-
dc.subject.MESHMacrophages/drug effects-
dc.subject.MESHMacrophages/immunology-
dc.subject.MESHMacrophages/metabolism-
dc.subject.MESHMice-
dc.subject.MESHNLR Family, Pyrin Domain-Containing 3 Protein-
dc.subject.MESHProtein Binding-
dc.subject.MESHProtein Transport-
dc.subject.MESHReactive Oxygen Species/metabolism-
dc.subject.MESHSTAT6 Transcription Factor/metabolism-
dc.subject.MESHSignal Transduction*/drug effects-
dc.subject.MESHTranscription, Genetic/drug effects-
dc.titleNon-transcriptional regulation of NLRP3 inflammasome signaling by IL-4-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Microbiology (미생물학)-
dc.contributor.googleauthorInhwa Hwang-
dc.contributor.googleauthorJungmin Yang-
dc.contributor.googleauthorSujeong Hong-
dc.contributor.googleauthorEun Ju Lee-
dc.contributor.googleauthorSeung-Hyo Lee-
dc.contributor.googleauthorTeresa Fernandes-Alnemri-
dc.contributor.googleauthorEmad S Alnemri-
dc.contributor.googleauthorJe-Wook Yu-
dc.identifier.doi10.1038/icb.2014.125-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA02508-
dc.relation.journalcodeJ01037-
dc.identifier.eissn1440-1711-
dc.identifier.pmid25601272-
dc.identifier.urlhttp://www.nature.com/icb/journal/v93/n6/full/icb2014125a.html-
dc.contributor.alternativeNameYu, Je Wook-
dc.contributor.affiliatedAuthorYu, Je Wook-
dc.rights.accessRightsnot free-
dc.citation.volume93-
dc.citation.number6-
dc.citation.startPage591-
dc.citation.endPage599-
dc.identifier.bibliographicCitationIMMUNOLOGY AND CELL BIOLOGY, Vol.93(6) : 591-599, 2015-
dc.identifier.rimsid30167-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers

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