NF-κB: a key role in inflammatory diseases

作者：Paul P. Tak, Gary S. Firestein · 发表于：Journal of Clinical Investigation · 年份：2001 · DOI：10.1172/jci11830 · 被引用次数：3912 · 研究领域：NF-κB Signaling Pathways、Immune Response and Inflammation、Cytokine Signaling Pathways and Interactions

NF-κB in defense and diseaseActivation of the NF-κB/Rel transcription family, by nuclear translocation of cytoplasmic complexes, plays a central role in inflammation through its ability to induce transcription of proinflammatory genes (1).This pathway is activated upon appropriate cellular stimulation, most often by signals related to pathogens or stress.Here we will discuss the specificity of various NF-κB proteins, their role in inflammatory disease, the regulation of NF-κB activity by IκB proteins and IκB kinase (IKK), and the development of therapeutic strategies aimed at inhibition of NF-κB. Functions of individual NF-κB proteins in immune cellsThe NF-κB/Rel family includes NF-κB1 (p50/p105), NF-κB2 (p52/p100), p65 (RelA), RelB, and c-Rel (2).Most members of this family (RelB being one exception) can homodimerize, as well as form heterodimers with each other.The most prevalent activated form of NF-κB is a heterodimer consisting of a p50 or p52 subunit and p65, which contains transactivation domains necessary for gene induction.Studies in knockout mice have shown distinct functions for different members of the NF-κB/Rel family.Various NF-κB proteins play a pivotal role in defense of the host against certain pathogens.Furthermore, lack of RelA leads to embryonic lethality and liver degeneration in knockout mice, whereas mice lacking p50 or RelB are immunodeficient but otherwise develop normally to adulthood.B cells from p50 knockout mice show abnormal mitogen responses and...