Bidirectional regulation of NF-κB by reactive oxygen species: A role of unfolded protein response

Nuclear factor-kappa B (NF-kappa B) is a transcription factor that plays a crucial role in coordinating innate and adaptive immunity, inflammation, and apoptotic cell death. NF-kappa B 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-kappa B by cytokines and lipopolysaccharides. However, recent studies also suggested that ROS have the potential to repress NF-kappa B activity. Currently, it is not well addressed how ROS regulate activity of NE-kappa B in a bidirectional fashion. In this paper, we summarize evidence for positive and negative regulation of NF-kappa B by ROS, possible redox-sensitive targets for NE-kappa B signaling, and mechanisms underlying biphasic and bidirectional influences of ROS on NF-kappa B, especially focusing on a role of ROS-mediated induction of endoplasmic reticulum stress. (C) 2013 Elsevier Inc. All rights reserved.