Nuclear Factor Kappa B Signaling Complexes in Acute Inflammation

Abstract

Significance: NF-κB is a master regulator of the inflammatory response and represents a key regulatory node in the complex inflammatory signaling network. Additionally, selective NF-κB transcriptional activity on specific target genes occurs through the control of redox-sensitive NF-κB interactions.Critical issues: NF-κB is a redox-sensitive transcription factor that forms specific signaling complexes to regulate selectively the expression of target genes in acute inflammation. Protein-protein interactions with co-regulatory proteins, other transcription factors, and chromatin remodelling proteins provide transcriptional specificity to NF-κB. Furthermore, different NF-κB subunits may form distinct redoxsensitive homo and heterodimers with distinct affinities for κB sites. Recent advances:The selective NF-κB response is mediated by redox-modulated NF-κB complexes with RPS3, PIR. CBP/p300, PGC-1, AP-1, STAT3, EGR-1 and SP-1. NF-κB is cooperatively co-activated with AP-1, STAT3, EGR-1 and SP-1 during the inflammatory process, whereas NF-κB complexes with CBP/p300 and PGC-1α regulates the expression of antioxidant genes. p65 and Nrf2 compete for binding to coactivator CBP/p300 playing opposite roles in the regulation of inflammatory genes. Snitrosylation or tyrosine nitration favors the recruitment of specific NF-κB subunits to κB sites. Future directions:Further research is required to elucidate the whole NF-κB interactome in order to fully characterize the complex NF-κB signalling network in redox signaling, inflammation, and cancer.

Modulation of Nrf2 and NF-κB Signaling Pathways by Naturally Occurring Compounds in Relation to Cancer Prevention and Therapy. Are Combinations Better Than Single Compounds?

“…In the nucleus, the active NF-κB complex binds to its target of the 5′-GGGRNYY YCC-3′ sequence [ 20 ] and connects with the basal transcriptional machinery. Its association among the others with AP-1 (c-Jun/c-Fos complex) and chromatin remodeling proteins, such as CREB-binding protein (CBP) and p300 is also possible [ 21 ].…”

Redox Homeostasis in Poultry: Regulatory Roles of NF-κB

“…NF-κB is known as a master regulator of the inflammatory response in the complex inflammatory network, playing a critical role in the host defense against pathogens, and it protects cells from apoptosis, as a result of triggering the upregulation of proinflammatory genes [ 386 ]. Furthermore, in acute inflammation, NF-κB, as a redox-sensitive transcription factor, was shown to participate in condition-dependent selective regulation of the expression of many target genes.…”

“…Furthermore, in acute inflammation, NF-κB, as a redox-sensitive transcription factor, was shown to participate in condition-dependent selective regulation of the expression of many target genes. They include proinflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-12), various antioxidants (e.g., glutamate cysteine ligase, SOD1, SOD2, and catalase) [ 386 ], proinflammatory enzymes (secretory phospholipase 2, sPLA2; COX-2, and iNOS), chemokines (macrophage inflammatory protein 1α (IP-1α), monocyte chemoattractant protein-1 (MCP1), growth factors, cell-cycle regulatory molecules, anti-inflammatory molecules, and adhesion molecules [ 387 ]. Under stress conditions, the NF-κB network is responsible for balancing the effect of various intracellular stress signals to maintain homeostasis and cell/tissue integrity [ 30 ].…”

Ferulic acid inhibits LPS-induced apoptosis in bovine mammary epithelial cells by regulating the NF-κB and Nrf2 signalling pathways to restore mitochondrial dynamics and ROS generation

“…The accumulated Nrf2 then transfers to the nucleus and interacts with antioxidant response elements (AREs) to address inflammation and oxidant stress [ 19 , 20 ]. In addition, Nrf2 and NF-κB competitively bind to the transcriptional coactivator cAMP-response-element-binding protein-binding protein (CBP) in the nucleus, playing opposite roles in regulating the expression of inflammatory genes [ 21 , 22 ]. The interplay between Nrf2 and NF-κB influences cellular responses to inflammation, oxidative stress and immunity, maintaining the stability of cell metabolism and the internal environment [ 15 , 23 , 24 ].…”