Figure 5.

Summary figure describing the crosstalk between Nrf2 and NF-κB. (1) Activation of IKK complex due to oxidative stress, which in turn phosphorylates NF-kB, leads to its translocation into the nucleus. In the nucleus, activation of proinflammatory cytokines such as COX-2, TNF-α, and IL-6 occurs, upregulating the inflammatory process. (2) SQ decreases the phosphorylated P65- NF-ƙB that subsequently leads to the downregulation of inflammatory process. (3) NF-kB combines with the competitive Nrf2 transcriptional co-activator CBP producing a terminal product, 15d-PGJ2. This molecule acts as an inducer of Nrf2, which reacts with KEAP1, causing the release of Nrf2 from KEAP1. (4) SQ increases total and phosphorylated Nrf2, which dimerize with a small Maf (sMaf) forming a heterodimer, ultimately binding to the ARE to induce gene transcription. (5) Activation of the Nrf2-Smaf-ARE combination activates the target gene expression for an antioxidant response, which ultimately leads to the suppression of oxidative stress. This figure is modified from Ahmed et al. (2017) [116].