Yamamoto Masahiro, Takeda Kiyoshi
Department of Microbiology and Immunology, Graduate School of Medicine, and WPI Immunology Frontier Research Center, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
J Infect Chemother. 2008 Aug;14(4):265-9. doi: 10.1007/s10156-008-0619-y. Epub 2008 Aug 17.
A variety of microbial components activate a transcription factor called nuclear factor-kappaB (NF-kappaB) that plays an essential role in the optimal activation of host immune systems. The transcriptional activity of NF-kappaB is tightly regulated at multiple steps in immune signaling pathways, because excessive activation is detrimental to the host. One mechanism to prevent NF-kappaB activation is mediated by cytoplasmic IkappaB family proteins. Although cytoplasmic IkappaBs interact with NF-kappaB subunits in the cytoplasm of unstimulated cells, IkappaBs are rapidly degraded on stimulation, allowing free NF-kappaB to translocate into the nucleus and activate the transcription of genes encoding various immune mediators. After the translocation of NF-kappaB from the cytoplasm to the nucleus, nuclear proteins that are structurally similar to cytoplasmic IkappaBs take part in the regulation of NF-kappaB transcriptional activity, as activators or inhibitors, by associating with NF-kappaB subunits. Therefore, the regulatory IkappaB-like nuclear molecules are described as "nuclear IkappaB proteins." In this review, the in vivo function of the nuclear IkappaB proteins, Bcl-3, IkappaBzeta, and IkappaBNS in the context of host immune responses and diseases will be discussed.
多种微生物成分可激活一种名为核因子-κB（NF-κB）的转录因子，它在宿主免疫系统的最佳激活中发挥着至关重要的作用。NF-κB的转录活性在免疫信号通路的多个步骤中受到严格调控，因为过度激活对宿主有害。一种防止NF-κB激活的机制是由细胞质中的IκB家族蛋白介导的。虽然细胞质中的IκB在未受刺激的细胞细胞质中与NF-κB亚基相互作用，但IκB在受到刺激后会迅速降解，使游离的NF-κB能够转运到细胞核中并激活编码各种免疫介质的基因的转录。在NF-κB从细胞质转运到细胞核后，结构上与细胞质IκB相似的核蛋白通过与NF-κB亚基结合，作为激活剂或抑制剂参与NF-κB转录活性的调节。因此，这些具有调节作用的类IκB核分子被称为“核IκB蛋白”。在这篇综述中，将讨论核IκB蛋白Bcl-3、IκBζ和IκBNS在宿主免疫反应和疾病背景下的体内功能。
