IκBζ controls NLRP3 inflammasome activation via upregulation of the Nlrp3 gene

被引:11
作者
Kim, Jeongeun [1 ,2 ]
Ahn, Huijeong [1 ,2 ]
Yu, Sangjung [1 ,2 ]
Ahn, Jae-Hee [3 ]
Ko, Hyun-Jeong [3 ]
Kweon, Mi-Na [4 ]
Hong, Eui-Ju [5 ,6 ]
An, Beum-Soo [7 ]
Lee, Eunsong [1 ,2 ]
Lee, Geun-Shik [1 ,2 ]
机构
[1] Kangwon Natl Univ, Coll Pharm, Coll Vet Med, Chunchon 24341, Gangwon, South Korea
[2] Kangwon Natl Univ, Coll Pharm, Inst Vet Sci, Chunchon 24341, Gangwon, South Korea
[3] Kangwon Natl Univ, Coll Pharm, Lab Microbiol & Immunol, Chunchon 24341, Gangwon, South Korea
[4] Univ Ulsan, Coll Med, Asan Med Ctr, Mucosal Immunol Lab,Dept Convergence Med, Seoul 05505, South Korea
[5] Chungnam Natl Univ, Coll Vet Med, Daejeon 34134, South Korea
[6] Chungnam Natl Univ, Inst Vet Sci, Daejeon 34134, South Korea
[7] Pusan Natl Univ, Coll Nat Resources & Life Sci, Dept Biomat Sci, Gyeongsangnam Do 50612, South Korea
基金
新加坡国家研究基金会;
关键词
Inflammasome; I kappa B zeta; Nfkbiz; Macrophages; Priming step; INHIBITS NLRP3; AIM2; EXPRESSION; PROTEIN; NLRC4; ACID;
D O I
10.1016/j.cyto.2019.154983
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Inflammasome activation induces the maturation and secretion of interleukin (IL)-1 beta and -18, and is dependent on NF-kappa B signaling to induce the transcription of the inflammasome components, called the priming step. This study elucidated the role of I kappa B zeta, an atypical l kappa Bs (inhibitor of kappa B) and a coactivator of NF-kappa B target genes, on the activation of inflammasome. Bone marrow-derived macrophages (BMDMs) that originated from I kappa B zeta-encoding Nfkbiz gene depletion mice presented a defect in NLRP3 inflammasome activation. In addition, the Nfkbiz(+/-) and Nfkbiz(-/-) mice significantly attenuated serum IL-1 beta secretion in response to a monosodium urate injection, a NLRP3 trigger, when compared with Nfkbiz(-/-) mice. The lack of I kappa B zeta in BMDMs produced a disability in the expression of Nlrp3 and pro-il1 beta mRNAs during the priming step. In addition, ectopic I kappa B zeta expression enhanced the Nlrp3 promoter activity, and Nlrp3 and pro-il1 beta transcription. Overall, I kappa B zeta controlled the activation of NLRP3 inflammasome by upregulating the Nlrp3 gene during the priming step.
引用
收藏
页数:8
相关论文
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