Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Cyclooxygenase-2 (COX-2) signaling pathway (NF-κB/COX-2 pathway)

The NF-κB/COX-2 signaling pathway is a fundamental regulatory axis in the inflammatory response, where the transcription factor NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) directly controls the expression of the COX-2 (Cyclooxygenase-2) enzyme (StatPearls, 2023). Under physiological conditions, NF-κB is sequestered in the cytoplasm; however, pro-inflammatory stimuli trigger its translocation to the nucleus, where it binds to the PTGS2 promoter to induce COX-2 synthesis (PubMed, PMC2824450). COX-2 then converts arachidonic acid into prostaglandins, which are key mediators of pain, fever, and inflammation (UniProt, P35354). This pathway is frequently dysregulated in chronic inflammatory diseases and various cancers, contributing to tumor cell proliferation, survival, and angiogenesis (Nature Reviews Cancer, 2002). Pharmacological modulation of this axis is achieved through selective COX-2 inhibitors (e.g., Celecoxib) that block enzymatic activity, or through agents like corticosteroids and proteasome inhibitors that suppress NF-κB activation, thereby reducing the overall inflammatory burden (NIH, 2022).

Other names

NF-kappaB/COX-2 axisNF-kappaB-mediated COX-2 inductionPTGS2 expression pathwayNF-kappaB/PTGS2 axis

Drugs target this pathway by either directly inhibiting the COX-2 enzyme's catalytic site (e.g., coxibs) or by preventing the nuclear translocation and transcriptional activity of NF-κB (e.g., corticosteroids, IKK inhibitors), thereby blocking the de novo synthesis of COX-2 protein and subsequent pro-inflammatory prostaglandins.