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Free Radic Biol Med. 2013 Dec;65:162-74. doi: 10.1016/j.freeradbiomed.2013.06.020. Epub 2013 Jun 19.

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

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  • 1Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi 409-3898, Japan.


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.

Copyright © 2013 Elsevier Inc. All rights reserved.


78-kDa glucose-regulated protein (BiP); ATF6; C/EBPβ; CCAAT/enhancer-binding protein homologous protein; CCAAT/enhancer-binding protein β; CHOP; DHMEQ; ER; ER stress response element; ER-associated degradation; ERAD; ERSE; Endoplasmic reticulum stress; GRP78; H/R; HDAC; HO-1; IKK; IL-1R; IRE1; IκB; IκB kinase; Keap-1; Kelch-like ECH-associated protein 1; LPS; NEMO; NF-κB; NF-κB essential modulator; NF-κB inducing kinase; NIK; Nrf2; PERK; PI3K; PKAc; PKB; PKD; PKR-like ER kinase; PP2A; RIP1; Reactive oxygen species; S1P; SH2-containing inositol 5′-phosphatase 1; SHIP-1; TNF receptor-associated factor; TNFR; TRAF; UPR; UPR element; UPRE; UV; Unfolded protein response; X-box-binding protein 1; XBP1; activating transcription factor 6; dehydroxymethylepoxyquinomicin; eIF2α; endoplasmic reticulum; eukaryotic translation initiation factor 2α; heme oxygenase 1; histone deacetylase; hypoxia/reoxygenation; inhibitor of NF-κB; inositol-requiring enzyme 1; interleukin-1 receptor; lipopolysaccharide; mTORC1; mammalian target of rapamycin complex 1; nuclear factor-E2-related factor 2; nuclear factor-κB; phosphatidylinositol 3-kinase; protein kinase A catalytic subunit; protein kinase B (Akt); protein kinase D; protein phosphatase 2A; receptor interacting protein 1; site-1 protease; tumor necrosis factor receptor; ultraviolet; unfolded protein response

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