Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 김현석 | - |
dc.date.accessioned | 2022-02-22T16:31:03Z | - |
dc.date.available | 2022-02-22T16:31:03Z | - |
dc.date.issued | 2021 | - |
dc.identifier.issn | 1664-3224 | - |
dc.identifier.other | OAK-30796 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/260595 | - |
dc.description.abstract | Nicotinamide adenine dinucleotide (NAD(+)) is an important cofactor in many redox and non-redox NAD(+)-consuming enzyme reactions. Intracellular NAD(+) level steadily declines with age, but its role in the innate immune potential of myeloid cells remains elusive. In this study, we explored whether NAD(+) depletion by FK866, a highly specific inhibitor of the NAD salvage pathway, can affect pattern recognition receptor-mediated responses in macrophages. NAD(+)-depleted mouse bone marrow-derived macrophages (BMDMs) exhibited similar levels of proinflammatory cytokine production in response to LPS or poly (I:C) stimulation compared with untreated cells. Instead, FK866 facilitated robust caspase-1 activation in BMDMs in the presence of NLRP3-activating signals such as ATP and nigericin, a potassium ionophore. However, this FK866-mediated caspase-1 activation was completely abolished in Nlrp3-deficient macrophages. FK866 plus nigericin stimulation caused an NLRP3-dependent assembly of inflammasome complex. In contrast, restoration of NAD(+) level by supplementation with nicotinamide mononucleotide abrogated the FK866-mediated caspase-1 cleavage. FK866 did not induce or increase the expression levels of NLRP3 and interleukin (IL)-1 beta but drove mitochondrial retrograde transport into the perinuclear region. FK866-nigericin-induced mitochondrial transport is critical for caspase-1 cleavage in macrophages. Consistent with the in vitro experiments, intradermal coinjection of FK866 and ATP resulted in robust IL-1 beta expression and caspase-1 activation in the skin of wild-type, but not Nlrp3-deficient mice. Collectively, our data suggest that NAD(+) depletion provides a non-transcriptional priming signal for NLRP3 activation via mitochondrial perinuclear clustering, and aging-associated NAD(+) decline can trigger NLRP3 inflammasome activation in ATP-rich environments. | - |
dc.language | English | - |
dc.publisher | FRONTIERS MEDIA SA | - |
dc.subject | NAD | - |
dc.subject | aging | - |
dc.subject | macrophage | - |
dc.subject | proinflammatory | - |
dc.subject | inflammasome | - |
dc.title | Intracellular NAD(+) Depletion Confers a Priming Signal for NLRP3 Inflammasome Activation | - |
dc.type | Article | - |
dc.relation.volume | 12 | - |
dc.relation.index | SCIE | - |
dc.relation.index | SCOPUS | - |
dc.relation.journaltitle | FRONTIERS IN IMMUNOLOGY | - |
dc.identifier.doi | 10.3389/fimmu.2021.765477 | - |
dc.identifier.wosid | WOS:000738847400001 | - |
dc.identifier.scopusid | 2-s2.0-85122124755 | - |
dc.author.google | Shim, Do-Wan | - |
dc.author.google | Cho, Hyo-Joung | - |
dc.author.google | Hwang, Inhwa | - |
dc.author.google | Jung, Taek-Yeol | - |
dc.author.google | Kim, Hyun-Seok | - |
dc.author.google | Ryu, Ju Hee | - |
dc.author.google | Yu, Je-Wook | - |
dc.contributor.scopusid | 김현석(57191717681) | - |
dc.date.modifydate | 20230201113042 | - |