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+/- and Nfkbiz-/- mice significantly attenuated serum IL-1β secretion in response to a monosodium urate injection, a NLRP3 trigger, when compared with Nfkbiz-+/+ 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.

中文翻译：

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IκBζ 通过上调 Nlrp3 基因控制 NLRP3 炎症小体激活

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-κB 信号传导诱导炎症小体成分的转录，称为启动步骤。本研究阐明了 IκBζ（一种非典型 IκB（κB 抑制剂）和 NF-κB 靶基因的共激活剂）对炎症小体激活的作用。源自编码 IκBζ 的 Nfkbiz 基因耗竭小鼠的骨髓源性巨噬细胞 (BMDM) 在 NLRP3 炎症小体激活方面存在缺陷。此外，与 Nfkbiz-+/+ 小鼠相比，Nfkbiz+/- 和 Nfkbiz-/- 小鼠显着减弱了血清 IL-1β 的分泌，以响应尿酸钠注射液（一种 NLRP3 触发器）。BMDM 中 IκBζ 的缺乏导致 Nlrp3 和 pro-Il1β mRNA 在启动步骤中的表达障碍。此外，异位 IκBζ 表达增强了 Nlrp3 启动子活性，以及​​ Nlrp3 和 pro-Il1β 转录。总体而言，IκBζ 通过在引发步骤中上调 Nlrp3 基因来控制 NLRP3 炎症小体的激活。