Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi 409-3898, Japan.
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi 409-3898, Japan.
Free Radic Biol Med. 2013 Dec;65:162-174. doi: 10.1016/j.freeradbiomed.2013.06.020. Epub 2013 Jun 19.
Nuclear factor-κB (NF-κB) is a transcription factor that plays a crucial role in coordinating innate and adaptive immunity, inflammation, and apoptotic cell death. NF-κB is activated by various inflammatory stimuli including peptide factors and infectious microbes. It is also known as a redox-sensitive transcription factor activated by reactive oxygen species (ROS). Over the past decades, various investigators focused on the role of ROS in the activation of NF-κB by cytokines and lipopolysaccharides. However, recent studies also suggested that ROS have the potential to repress NF-κB activity. Currently, it is not well addressed how ROS regulate activity of NF-κB in a bidirectional fashion. In this paper, we summarize evidence for positive and negative regulation of NF-κB by ROS, possible redox-sensitive targets for NF-κB signaling, and mechanisms underlying biphasic and bidirectional influences of ROS on NF-κB, especially focusing on a role of ROS-mediated induction of endoplasmic reticulum stress.
核因子-κB（NF-κB）是一种转录因子，在协调先天和适应性免疫、炎症和凋亡细胞死亡方面发挥着关键作用。NF-κB 可被多种炎症刺激物激活，包括肽因子和感染性微生物。它也被称为一种由活性氧（ROS）激活的氧化还原敏感转录因子。在过去的几十年中，许多研究人员专注于 ROS 在细胞因子和脂多糖激活 NF-κB 中的作用。然而，最近的研究还表明，ROS 有可能抑制 NF-κB 的活性。目前，ROS 如何以双向方式调节 NF-κB 的活性还没有得到很好的解决。在本文中，我们总结了 ROS 对 NF-κB 的正向和负向调节、NF-κB 信号的可能氧化还原敏感靶标，以及 ROS 对 NF-κB 的双相和双向影响的机制，特别是聚焦于 ROS 介导的内质网应激诱导在其中的作用。
