IκBζ controls NLRP3 inflammasome activation via upregulation of the Nlrp3 gene
IκBζ controls NLRP3 inflammasome activation via upregulation of the Nlrp3 gene
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DOI：
10.1016/j.cyto.2019.154983
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发表时间：
2020-03-01
期刊：
影响因子：
3.8
通讯作者：
Lee, Geun-Shik
中科院分区：
文献类型：
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作者：
Kim, Jeongeun;Ahn, Huijeong;Lee, Geun-Shik
炎症小体激活诱导白细胞介素 (IL)-1β 和 -18 的成熟和分泌，并依赖 NF-κ B 信号传导诱导炎症小体成分的转录，称为启动步骤。这项研究阐明了 I kappa B zeta（一种非典型 l kappa Bs（kappa B 抑制剂）和 NF-kappa B 靶基因的共激活剂）在炎症小体激活中的作用。源自 I kappa B zeta 编码 Nfkbiz 基因缺失小鼠的骨髓源性巨噬细胞 (BMDM) 在 NLRP3 炎性体激活中存在缺陷。此外，与 Nfkbiz(-/-) 小鼠相比，Nfkbiz(+/-) 和 Nfkbiz(-/-) 小鼠响应尿酸钠注射（NLRP3 触发因素），血清 IL-1 β 分泌显着减弱。 BMDM 中 I kappa B zeta 的缺乏导致在启动步骤中 Nlrp3 和 pro-il1 beta mRNA 的表达出现障碍。此外，异位 I kappa B zeta 表达增强了 Nlrp3 启动子活性以及 Nlrp3 和 pro-il1 beta 转录。总体而言，I kappa B zeta 通过在启动步骤中上调 Nlrp3 基因来控制 NLRP3 炎症小体的激活。
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.