PMID- 31918161 OWN - NLM STAT- MEDLINE DCOM- 20210818 LR - 20210818 IS - 1096-0023 (Electronic) IS - 1043-4666 (Linking) VI - 127 DP - 2020 Mar TI - IkappaBzeta controls NLRP3 inflammasome activation via upregulation of the Nlrp3 gene. PG - 154983 LID - S1043-4666(19)30415-6 [pii] LID - 10.1016/j.cyto.2019.154983 [doi] AB - Inflammasome activation induces the maturation and secretion of interleukin (IL)-1beta and -18, and is dependent on NF-kappaB signaling to induce the transcription of the inflammasome components, called the priming step. This study elucidated the role of IkappaBzeta, an atypical IkappaBs (inhibitor of kappaB) and a coactivator of NF-kappaB target genes, on the activation of inflammasome. Bone marrow-derived macrophages (BMDMs) that originated from IkappaBzeta-encoding Nfkbiz gene depletion mice presented a defect in NLRP3 inflammasome activation. In addition, the Nfkbiz(+/-) and Nfkbiz(-/-) mice significantly attenuated serum IL-1beta secretion in response to a monosodium urate injection, a NLRP3 trigger, when compared with Nfkbiz(-+/+) mice. The lack of IkappaBzeta in BMDMs produced a disability in the expression of Nlrp3 and pro-Il1beta mRNAs during the priming step. In addition, ectopic IkappaBzeta expression enhanced the Nlrp3 promoter activity, and Nlrp3 and pro-Il1beta transcription. Overall, IkappaBzeta controlled the activation of NLRP3 inflammasome by upregulating the Nlrp3 gene during the priming step. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Kim, Jeongeun AU - Kim J AD - College of Veterinary Medicine and Institute of Veterinary Science, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea. FAU - Ahn, Huijeong AU - Ahn H AD - College of Veterinary Medicine and Institute of Veterinary Science, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea. FAU - Yu, Sangjung AU - Yu S AD - College of Veterinary Medicine and Institute of Veterinary Science, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea. FAU - Ahn, Jae-Hee AU - Ahn JH AD - Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea. FAU - Ko, Hyun-Jeong AU - Ko HJ AD - Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea. FAU - Kweon, Mi-Na AU - Kweon MN AD - Mucosal Immunology Laboratory, Department of Convergence Medicine, University of Ulsan College of Medicine/Asan Medical Center, Seoul 05505, Republic of Korea. FAU - Hong, Eui-Ju AU - Hong EJ AD - College of Veterinary Medicine and Institute of Veterinary Science, Chungnam National University, Daejeon 34134, Republic of Korea. FAU - An, Beum-Soo AU - An BS AD - Department of Biomaterial Science, College of Natural Resources and Life Science, Pusan National University, Gyeongsangnam-do 50612, Republic of Korea. FAU - Lee, Eunsong AU - Lee E AD - College of Veterinary Medicine and Institute of Veterinary Science, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea. FAU - Lee, Geun-Shik AU - Lee GS AD - College of Veterinary Medicine and Institute of Veterinary Science, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea. Electronic address: leegeun@kangwon.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200107 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Inflammasomes) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (Nfkbiz protein, mouse) RN - 0 (Nlrp3 protein, mouse) RN - 0 (RNA, Messenger) SB - IM MH - Adaptor Proteins, Signal Transducing/*genetics MH - Animals MH - Cells, Cultured MH - Inflammasomes/*genetics MH - Macrophages/metabolism MH - Mice MH - NLR Family, Pyrin Domain-Containing 3 Protein/*genetics MH - Promoter Regions, Genetic/genetics MH - RAW 264.7 Cells MH - RNA, Messenger/genetics MH - Signal Transduction/genetics MH - Transcription, Genetic/genetics MH - Up-Regulation/*genetics OTO - NOTNLM OT - Inflammasome OT - IkappaBzeta OT - Macrophages OT - Nfkbiz OT - Priming step COIS- 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. EDAT- 2020/01/10 06:00 MHDA- 2021/08/19 06:00 CRDT- 2020/01/10 06:00 PHST- 2019/08/14 00:00 [received] PHST- 2019/12/12 00:00 [revised] PHST- 2019/12/31 00:00 [accepted] PHST- 2020/01/10 06:00 [pubmed] PHST- 2021/08/19 06:00 [medline] PHST- 2020/01/10 06:00 [entrez] AID - S1043-4666(19)30415-6 [pii] AID - 10.1016/j.cyto.2019.154983 [doi] PST - ppublish SO - Cytokine. 2020 Mar;127:154983. doi: 10.1016/j.cyto.2019.154983. Epub 2020 Jan 7.