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IκBζ controls NLRP3 inflammasome activation via upregulation of the Nlrp3 gene.
- Source :
-
Cytokine [Cytokine] 2020 Mar; Vol. 127, pp. 154983. Date of Electronic Publication: 2020 Jan 07. - Publication Year :
- 2020
-
Abstract
- Inflammasome activation induces the maturation and secretion of interleukin (IL)-1β and -18, and is dependent on NF-κB signaling to induce the transcription of the inflammasome components, called the priming step. This study elucidated the role of IκBζ, an atypical IκBs (inhibitor of κB) and a coactivator of NF-κB target genes, on the activation of inflammasome. Bone marrow-derived macrophages (BMDMs) that originated from IκBζ-encoding Nfkbiz gene depletion mice presented a defect in NLRP3 inflammasome activation. In addition, the Nfkbiz <superscript>+/-</superscript> and Nfkbiz <superscript>-/-</superscript> mice significantly attenuated serum IL-1β secretion in response to a monosodium urate injection, a NLRP3 trigger, when compared with Nfkbiz <superscript>-+/+</superscript> mice. The lack of IκBζ in BMDMs produced a disability in the expression of Nlrp3 and pro-Il1β mRNAs during the priming step. In addition, ectopic IκBζ expression enhanced the Nlrp3 promoter activity, and Nlrp3 and pro-Il1β transcription. Overall, IκBζ controlled the activation of NLRP3 inflammasome by upregulating the Nlrp3 gene during the priming step.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Cells, Cultured
Macrophages metabolism
Mice
Promoter Regions, Genetic genetics
RAW 264.7 Cells
RNA, Messenger genetics
Signal Transduction genetics
Transcription, Genetic genetics
Adaptor Proteins, Signal Transducing genetics
Inflammasomes genetics
NLR Family, Pyrin Domain-Containing 3 Protein genetics
Up-Regulation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0023
- Volume :
- 127
- Database :
- MEDLINE
- Journal :
- Cytokine
- Publication Type :
- Academic Journal
- Accession number :
- 31918161
- Full Text :
- https://doi.org/10.1016/j.cyto.2019.154983