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Antioxidants & Redox Signaling
PMC full text:

FIG. 15.

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NF-κB and Nrf2, the Yin and Yang of the inflammatory response. Occupation of receptors by pathogen-associated molecular patterns, damage-associated molecular pattern (DAMPs), TNFα, or IL-1 leads to superoxide formation in the redoxosome by NOX. H2O2 formed by SOD favors activation of NF-κB at multiple sites though enhancing protein phosphorylation, but also oxidizes Keap1 in the Nrf2 system. While NF-κB tends to enhance and perpetuate the inflammatory response by triggering the expression of pro-inflammatory cytokines, Nrf2 activation through Keap1 oxidation dampens pro-inflammatory signaling by expression of peroxidases and other anti-inflammatory proteins. As E3-ligase, Keap1 also primes IKKβ to degradation via ubiquitination, thereby directly interfering with NF-κB activation. For sake of clarity, only NOX-derived H2O2 is shown as oxidant signal. Depending on the cellular system and the inflammatory stimulus, NOX-derived H2O2 may be supported or replaced by mitochondrial H2O2, lipoxygenase products, and S-alkylating electrophiles derived there from.

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