Figure 1.

Intranuclear signal transductions can occur in two different pathways: while nuclear factor kappaB (NF-κB) tends to enhance and perpetuate the inflammatory response by triggering the expression of pro-inflammatory cytokines, nuclear factor erythroid 2–related factor 2 (Nrf2) activation through Kelch-like ECH-associated protein-1 (Keap1) oxidation dampens pro-inflammatory signaling by expression of peroxidases and other anti-inflammatory proteins. As E3-ligase, Keap1 also primes inhibitor of NF-κB kinase subunit beta (IKKβ) to degradation via ubiquitination, thereby directly interfering with NF-κB activation. For the sake of clarity, only the reactive oxygen species (ROS)-producing enzyme NADPH oxidase (NOX)-derived H2O2 is shown as an 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 therefrom. NEMO, NF-κB essential modulator; IκB, Inhibitor of NF-κB.