Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) mediated transcription of Cyclooxygenase-2 (COX-2) and 5-Lipoxygenase (5-LOX) (NF-κB/COX-2/5-LOX axis)

The NF-κB-mediated transcription of COX-2 and 5-LOX is a critical regulatory axis in the inflammatory response, linking the activation of the master transcription factor NF-κB to the production of key eicosanoid-producing enzymes. NF-κB (Nuclear Factor-kappa B) is activated by various pro-inflammatory stimuli, such as cytokines (TNF-α, IL-1β) and oxidative stress, leading to its translocation into the nucleus where it binds to the promoter regions of the PTGS2 (encoding COX-2) and ALOX5 (encoding 5-LOX) genes [1, 2]. COX-2 and 5-LOX are the rate-limiting enzymes in the synthesis of prostaglandins and leukotrienes, respectively, which are potent mediators of pain, fever, vascular permeability, and bronchoconstriction [3]. This pathway is highly relevant in chronic inflammatory conditions such as rheumatoid arthritis, asthma, and inflammatory bowel disease, and its dysregulation is also a hallmark of cancer progression where chronic inflammation promotes tumor growth and survival [4]. Therapeutic strategies targeting this axis include the use of corticosteroids to suppress NF-κB activity or the development of dual COX/5-LOX inhibitors, such as licofelone, which aim to provide a more comprehensive anti-inflammatory effect with potentially fewer side effects than traditional NSAIDs by preventing the "leukotriene shunt" [5]. Sources: [1] Tak PP, Firestein GS. J Clin Invest. 2001; [2] Martel-Pelletier J, et al. Ann Rheum Dis. 2003; [3] Singh VP, et al. Biol Pharm Bull. 2010; [4] Karin M. Mol Cancer Ther. 2006; [5] Celec P. Biomed Pharmacother. 2004.

Other names

NF-kappaB/COX-2/5-LOX pathwayArachidonic acid metabolism regulation by NF-kBPro-inflammatory gene transcription axisNF-kB-mediated eicosanoid synthesis

Inhibition of NF-κB nuclear translocation or DNA binding, thereby preventing the transcriptional induction of PTGS2 (COX-2) and ALOX5 (5-LOX) enzymes, or direct dual inhibition of the enzymes themselves.