Pro-inflammatory and antioxidant signaling pathways

Pro-inflammatory and antioxidant signaling pathways encompass a complex regulatory network essential for cellular adaptation to stress and injury. The pro-inflammatory arm, primarily mediated by the NF-κB and MAPK pathways, triggers the expression of genes involved in the innate and adaptive immune responses (Oeckinghaus & Ghosh, 2009, Cold Spring Harb Perspect Biol). Simultaneously, the antioxidant arm, centered on the Nrf2-Keap1 axis, regulates the expression of cytoprotective genes that neutralize reactive oxygen species and electrophiles (Ma, 2013, Physiol Rev). A delicate balance between these pathways is required for health; chronic overactivation of inflammatory signaling or suppression of antioxidant defenses leads to oxidative stress and tissue damage. This imbalance is a fundamental driver of various pathologies, including cardiovascular disease, neurodegeneration, and cancer (Wardyn et al., 2015, Free Radic Biol Med). Therapeutic agents like dimethyl fumarate and various polyphenols aim to modulate this balance by inhibiting inflammatory mediators or enhancing antioxidant capacity. For example, dimethyl fumarate is used in multiple sclerosis to reduce inflammation and provide neuroprotection through Nrf2 activation (Linker et al., 2011, Brain). However, the broad involvement of these pathways in normal physiology poses challenges for drug specificity and safety. Potential risks include systemic immunosuppression or the unintended promotion of survival in malignant cells, requiring precise targeting of specific nodes within the network.

Other names

Inflammatory and oxidative stress pathwaysRedox signaling pathwaysPro-inflammatory/antioxidant axisNrf2/NF-κB crosstalkInflammation and antioxidant response elements

Drugs typically modulate these pathways by inhibiting pro-inflammatory transcription factors, such as Nuclear Factor-kappa B (NF-κB), to reduce the production of inflammatory cytokines, or by activating the Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to enhance the expression of antioxidant and cytoprotective enzymes (Wardyn et al., 2015, Free Radic Biol Med).