Noncanonical NF-κB activation and SDF-1 expression in human endothelial cells.
Noncanonical NF-κB activation and SDF-1 expression in human endothelial cells.
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人内皮细胞中的非经典 NF-κB 激活和 SDF-1 表达。
DOI：
10.1007/978-1-4939-2422-6_9
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
May,MichaelJ
中科院分区：
文献类型：
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作者：
McCorkell,KellyA;May,MichaelJ
NF-κB是一个转录因子家族，通过两种不同的信号级联调控，即经典的和非典型的NF-κB通路。非典型NF-κB在免疫系统中发挥着重要作用，它是淋巴器官发生和b细胞存活、分化以及破骨细胞发生所必需的。在过去的几年中，越来越多的研究关注于确定非典型NF-κB通路的上游调控事件，以及确定非典型NF-κB在正常和疾病病理（如癌症和自身免疫性疾病）中的生理作用。非典型NF-κB的失调与几种类型的淋巴瘤和自身免疫性疾病的发病机制有关，并被认为与慢性炎症性疾病有关，包括溃疡性结肠炎。这些研究表明，针对非典型途径，类似于经典的NF-κB，可能在未来有一定的治疗潜力；然而，关于非规范信号的调控仍有相当多的内容有待定义。在本章中，我们将描述HUVEC作为一种体外模型的使用，用于检测不同刺激下非典型NF-κB信号传导。我们展示了两种不同的方法来测量非典型NF-κB激活：p100到p52的加工，以及CXCL12非典型NF-κB依赖性基因的表达。第一种方法研究了非典型NF-κB激活的关键调控要求，p100通过蛋白水解裂解来减轻NF-κB二聚体对核易位和基因转录激活的抑制。后者表明活化的非典型NF-κB在刺激反应中的下游作用。
NF-κB is a family of transcription factors regulated through two distinct signaling cascades, the classical and the Noncanonical NF-κB pathways. Noncanonical NF-κB plays important roles in the immune system, as it is necessary for lymphoid organogenesis and B-cell survival and differentiation, as well as osteoclastogenesis. In the last few years, there has been an increased number of studies focusing on both identifying the upstream events that regulate the noncanonical NF-κB pathway as well as determining the physiological roles of noncanonical NF-κB in normal and disease pathologies, such as cancer and autoimmune diseases. Dysregulation of noncanonical NF-κB has now been associated with the pathogenesis of several types of lymphomas and autoimmune diseases and is believed to contribute to chronic inflammatory diseases, including ulcerative colitis. These studies suggest that targeting the Noncanonical pathway, similar to classical NF-κB, may have some therapeutic potential in the future; however, there is still quite a bit about the regulation of the noncanonical signaling that remains to be defined. In this chapter we describe the use of HUVEC, as an in vitro model for examining noncanonical NF-κB signaling in response to different stimuli. We demonstrate two different methods to measure noncanonical NF-κB activation: the processing of p100 to p52, and noncanonical NF-κB-dependent gene expression of CXCL12. The first method examines a key regulatory requirement for noncanonical NF-κB activation, by which p100 undergoes proteolytic cleavage to relieve the inhibition of NF-κB dimers for nuclear translocation and activation of gene transcription. The latter demonstrates the downstream effects of activated noncanonical NF-κB in response to stimuli.