Neonatal Brain Injury Laboratory, Division of Biomedical Research, Nemours Children's Health, Wilmington, DE 19803, USA.
Division of Neurology, Department of Pediatrics, Nemours Children's Health, Wilmington, DE 19803, USA.
Cells. 2024 Mar 11;13(6):485. doi: 10.3390/cells13060485.
The NF-κB (nuclear factor K-light-chain-enhancer of activated B cells) transcription factor family is critical for modulating the immune proinflammatory response throughout the body. During the resting state, inactive NF-κB is sequestered by IκB in the cytoplasm. The proteasomal degradation of IκB activates NF-κB, mediating its translocation into the nucleus to act as a nuclear transcription factor in the upregulation of proinflammatory genes. Stimuli that initiate NF-κB activation are diverse but are canonically attributed to proinflammatory cytokines and chemokines. Downstream effects of NF-κB are cell type-specific and, in the majority of cases, result in the activation of pro-inflammatory cascades. Acting as the primary immune responders of the central nervous system, microglia exhibit upregulation of NF-κB upon activation in response to pathological conditions. Under such circumstances, microglial crosstalk with other cell types in the central nervous system can induce cell death, further exacerbating the disease pathology. In this review, we will emphasize the role of NF-κB in triggering neuroinflammation mediated by microglia.
NF-κB（核因子 K 轻链增强子的 B 细胞）转录因子家族对于调节全身的免疫炎症反应至关重要。在静息状态下，非活性 NF-κB 被细胞质中的 IκB 隔离。IκB 的蛋白酶体降解激活 NF-κB，介导其易位到细胞核中，作为核转录因子上调促炎基因。启动 NF-κB 激活的刺激因素多种多样，但通常归因于促炎细胞因子和趋化因子。NF-κB 的下游效应具有细胞类型特异性，在大多数情况下，导致促炎级联反应的激活。作为中枢神经系统的主要免疫反应者，小胶质细胞在对病理条件的反应中被激活时，NF-κB 的表达上调。在这种情况下，小胶质细胞与中枢神经系统中其他细胞类型的相互作用会诱导细胞死亡，进一步加剧疾病病理学。在这篇综述中，我们将强调 NF-κB 在触发小胶质细胞介导的神经炎症中的作用。
