IκBζ controls NLRP3 inflammasome activation via upregulation of the Nlrp3 gene

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.