Studies on stimulus-specific induction of a novel NF-κB regulator, IκB-ζ, and its physiological roles

在静息的巨噬细胞中几乎检测不到IκB-ζ，并且在脂多糖（LPS）或白细胞介素(IL)-1β刺激下强烈诱导，而不是肿瘤坏死因子(TNF)-α。诱导的i -κB -ζ与细胞核中的NF-κB结合，并根据基因的启动子结构对其转录活性进行正向和负向调节。在本研究中，我们研究了决定i -κB -ζ不同功能的机制，并发现在toll样受体或IL-1受体的刺激下，i -κB -ζ在含有NF-κB和C/EBP结合位点的启动子上与NF-κB形成复合物，从而起到重要的转录激活作用。我们还分析了IκB-ζ差异诱导的分子机制，发现IκB-ζ mRNA的稳定性在LPS或IL-1β而非TNF- α刺激下特异性上调，并且在IκB-ζ mRNA的3'- utr中存在165-bp片段，赋予刺激特异性诱导，并且对IκB-ζ的诱导至关重要。

IκB-ζ is barely detectable in resting macrophages and is strongly induced upon stimulation with lipolysaccharide(LPS) or Interleukin (IL)-1β but not tumor necrosis factor(TNF)-α. The induced IκB-ζ associates with the NF-κB submit in the nucleus and regulates its transcriptional activity both positively and negatively depending on promoter structures of genes. In the present study, we investigated mechanisms that determine the different functions of IκB-ζ and found that IκB-ζ acts as an essential transcriptional activation by forming a complex with NF-κB on promoters harboring the NF-κB and C/EBP binding sites, upon stimulation of Toll-Like receptors or IL-1 receptor. We also analyzed the molecular mechanisms for the differential induction of IκB-ζ and found that the stability of IκB-ζ mRNA is specifically upregulated by stimulation with LPS or IL-1β but not TNF- α and that a 165-bp fragment present in the 3'-UTR of IκB-ζ mRNA confers the stimulus-specific induction and is essential for the induction of IκB-ζ.