Redox-Sensitive Immune Pathways: Nrf2, NF-κB, and the Balance Between Inflammation and Cytoprotection
The balance between inflammation and cytoprotection in the immune system is critically regulated by redox- sensitive pathways - notably Nuclear factor erythroid- 2- related factor 2 (Nrf2) and Nuclear Factor kappa- light- chain- enhancer of activated B cells (NF-κB). Nrf2 orchestrates antioxidant and cytoprotective gene expression, safeguarding cells from oxidative and electrophilic stress, while NF-κB governs pro- inflammatory and immune- activating programs. The interplay - or “cross- talk” - between these pathways determines whether a cell mounts an inflammatory response or engages protective, redox- balanced processes. Excessive reactive oxygen species (ROS) can hyperactivate NF-κB, driving inflammation, tissue damage, and chronic disease; whereas Nrf2 activation restores redox homeostasis, suppressing NF-κB–mediated inflammation and promoting cellular resilience. This review discusses the molecular mechanisms regulating Nrf2 and NF-κB activation, their mutual regulation, and how their balance affects immune responses, inflammation, and cytoprotection. We explore how natural and pharmacologic agents modulate this balance, the implications for inflammatory diseases, tissue protection, and potential risks of disrupting redox- sensitive signaling. Recognizing the Nrf2–NF-κB balance as a central node in immunoregulation offers a refined framework for therapeutic strategies aiming to harness cytoprotection without impairing immune competence or triggering unchecked inflammation.