Nuclear factor kappa-light-chain-enhancer of activated B cells–Cyclooxygenase-2–Inducible nitric oxide synthase inflammatory signaling axis (NF-κB–COX-2–iNOS axis)

The NF-κB–COX-2–iNOS inflammatory signaling axis is a central regulatory pathway that coordinates the cellular response to pro-inflammatory stimuli, such as cytokines, lipopolysaccharides, and oxidative stress [PubMed: 11907462]. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) serves as the master transcription factor that, upon activation and translocation to the nucleus, induces the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) [UniProt: P35354, P35228]. These enzymes are responsible for the production of nitric oxide and prostaglandins, respectively, which are key mediators of inflammation, vasodilation, and pain [StatPearls: NBK499830]. Dysregulation of this axis is strongly linked to chronic inflammatory diseases, various cancers, and neurodegenerative disorders [PubMed: 21533447]. Pharmacological intervention often involves non-steroidal anti-inflammatory drugs (NSAIDs) that inhibit COX-2, or corticosteroids and natural polyphenols that suppress NF-κB activation to reduce the overall inflammatory burden [PubChem: CID 962]. This axis represents a major target for drug development aimed at treating conditions characterized by excessive inflammation and oxidative stress. Inhibition of this pathway helps in reducing tissue damage and alleviating symptoms associated with chronic inflammatory states. Overall, it remains a key focus in both basic research and clinical pharmacology for its broad impact on human health.

Other names

NF-κB–COX-2–iNOS inflammatory signaling axisNF-kappaB/COX-2/iNOS pathwayNF-κB/iNOS/COX-2 signaling cascadePro-inflammatory NF-κB-mediated axisNF-kappaB-dependent COX-2 and iNOS expression pathway

The mechanism involves the inhibition of the IκB kinase (IKK) complex to prevent NF-κB activation, the direct competitive or irreversible inhibition of the COX-2 active site, and the transcriptional repression or direct inhibition of the iNOS enzyme, collectively reducing the production of pro-inflammatory mediators [PubMed: 12490379, 15690313].