Table 1.

Possible mechanisms of Nrf2–NF-κB interactions.

Mechanisms of Nrf2–NF-κB Interactions	References
Inhibiting effects of Nrf2 on NF-κB
Decreasing the intracellular ROS levels. This inhibits oxidative stress-mediated NF-κB activation	[103]
Preventing the IκB-proteasomal degradation and inhibiting nuclear translocation of NF-κB. In Nrf2-deficient cells an inhibitor of NF-kB activity (IκB) is over-phosphorylated with rapid proteasomal degradation and increased NF-κB activity. Upregulation of Nrf2 induces increase heme oxygenase-1 (HO-1) levels and induce phase II enzymes expression blocking the degradation of IκB	[104,105,106,107]
Reducing p50 and p65 DNA binding. Nrf2 silencing enhanced p50 and p65 DNA binding and tumour necrosis factor (TNF)-α-induced proinflammatory gene expression	[108]
Preventing the recruitment of RNA polymerase II to start transcription of NF-κB-regulated genes. Nrf2 binds to regulatory regions of proinflammatory genes in an antioxidant-response element (ARE)-independent manner and prevents the recruitment of RNA polymerase II to start transcription of NF-κB-regulated genes	[109]
Competition between Nrf2 and p65 for binding to the transcriptional co-activator CBP-p300 complex. Overexpression of p65 limits the availability of CBR for Nrf2 interaction. Knockdown of p65 promotes Nrf2 complex formation with CBR	[110,111]
Degrading IKKβ through ubiquitination by Keap1	[112]
Inhibiting effects of NF-κB on Nrf2
Inactivating Nrf2 by inducing cyclooxygenase 2	[113,114]
Recruiting MAF BZIP Transcription Factor K (MafK)-associated histone deacetylase 3 (HDAC3) activity to the HO-1 enhancer and deacetylating CBP leading to a suppression of its co-activator activity	[115,116]
Interacting with CREB-binding protein, the competent Nrf2 coactivator, and inhibiting the transcription of genes regulated by Nrf2	[111,117,118]
Decreasing free CBP, a transcriptional co-activator of Nrf2, and promoting phosphorylation of p65. Overexpression of p65 limits the availability of CBR for Nrf2 interaction. Knockdown of p65 promotes Nrf2 complex formation with CBR	[111]
κB sites in proximal promoter of Nrf2 are believed to be subject to binding and transcription initiation by p65	[119]