The canonical NF-κB pathway instructs the expression of inflammatory genes by the RelA:p50 transcription factor in response to diverse cell-activating stimuli. However, this mainstay RelA:p50 transcriptional output must also be curated so as to provide for stimulus-type-specific and cell-type-specific inflammatory responses adapted to the local tissue-microenvironment. Here, we summarize the fundamental mechanisms regulating RelA:p50-mediated gene expressions and discuss how the NF-κB system imparts specificity in the inflammatory gene program. We put forward a conceptual framework where the dynamical attributes and the composition of the nuclear NF-κB complexes cumulatively instruct context-specific inflammatory gene patterns. We propose that integrating mechanistic knowledge and systems-level analyses may offer further insights on NF-κB-mediated inflammatory gene control in the future.

经典的 NF-κB 通路通过 RelA:p50 转录因子指示炎症基因的表达，以响应不同的细胞激活刺激。然而，这种主要的 RelA:p50 转录输出也必须进行管理，以便提供适应局部组织微环境的刺激类型特异性和细胞类型特异性炎症反应。在这里，我们总结了调节 RelA:p50 介导的基因表达的基本机制，并讨论了 NF-κB 系统如何在炎症基因程序中赋予特异性。我们提出了一个概念框架，其中核 NF-κB 复合物的动力学属性和组成累积指示上下文特定的炎症基因模式。