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IκBζ controls NLRP3 inflammasome activation via upregulation of the Nlrp3 gene.

Authors :
Kim J
Ahn H
Yu S
Ahn JH
Ko HJ
Kweon MN
Hong EJ
An BS
Lee E
Lee GS
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.)

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