DC Field | Value | Language |
---|---|---|
dc.contributor.author | Hwang, Inhwa | ko |
dc.contributor.author | Yang, Jungmin | ko |
dc.contributor.author | Hong, Sujeong | ko |
dc.contributor.author | Lee, Eun Ju | ko |
dc.contributor.author | Lee, Seung-Hyo | ko |
dc.contributor.author | Fernandes-Alnemri, Teresa | ko |
dc.contributor.author | Alnemri, Emad S. | ko |
dc.contributor.author | Yu, Je-Wook | ko |
dc.date.accessioned | 2015-07-29T01:43:27Z | - |
dc.date.available | 2015-07-29T01:43:27Z | - |
dc.date.created | 2015-04-08 | - |
dc.date.created | 2015-04-08 | - |
dc.date.issued | 2015-07 | - |
dc.identifier.citation | IMMUNOLOGY AND CELL BIOLOGY, v.93, no.6, pp.591 - 599 | - |
dc.identifier.issn | 0818-9641 | - |
dc.identifier.uri | http://hdl.handle.net/10203/200233 | - |
dc.description.abstract | Th2 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-1 beta 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-kappa B 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.language | English | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | CELL-DEATH | - |
dc.subject | ALTERNATIVE ACTIVATION | - |
dc.subject | RECEPTOR ANTAGONIST | - |
dc.subject | NALP3 INFLAMMASOME | - |
dc.subject | HUMAN MONOCYTES | - |
dc.subject | MACROPHAGES | - |
dc.subject | INTERLEUKIN-4 | - |
dc.subject | EXPRESSION | - |
dc.subject | DISEASE | - |
dc.subject | PYROPTOSOME | - |
dc.title | Non-transcriptional regulation of NLRP3 inflammasome signaling by IL-4 | - |
dc.type | Article | - |
dc.identifier.wosid | 000357605800011 | - |
dc.identifier.scopusid | 2-s2.0-84936847396 | - |
dc.type.rims | ART | - |
dc.citation.volume | 93 | - |
dc.citation.issue | 6 | - |
dc.citation.beginningpage | 591 | - |
dc.citation.endingpage | 599 | - |
dc.citation.publicationname | IMMUNOLOGY AND CELL BIOLOGY | - |
dc.identifier.doi | 10.1038/icb.2014.125 | - |
dc.contributor.localauthor | Lee, Seung-Hyo | - |
dc.contributor.nonIdAuthor | Hwang, Inhwa | - |
dc.contributor.nonIdAuthor | Yang, Jungmin | - |
dc.contributor.nonIdAuthor | Hong, Sujeong | - |
dc.contributor.nonIdAuthor | Lee, Eun Ju | - |
dc.contributor.nonIdAuthor | Fernandes-Alnemri, Teresa | - |
dc.contributor.nonIdAuthor | Alnemri, Emad S. | - |
dc.contributor.nonIdAuthor | Yu, Je-Wook | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | CELL-DEATH | - |
dc.subject.keywordPlus | ALTERNATIVE ACTIVATION | - |
dc.subject.keywordPlus | RECEPTOR ANTAGONIST | - |
dc.subject.keywordPlus | NALP3 INFLAMMASOME | - |
dc.subject.keywordPlus | HUMAN MONOCYTES | - |
dc.subject.keywordPlus | MACROPHAGES | - |
dc.subject.keywordPlus | INTERLEUKIN-4 | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | DISEASE | - |
dc.subject.keywordPlus | PYROPTOSOME | - |
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