Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and pro-inflammatory cytokines (NF-κB/Cytokines)

Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a pivotal transcription factor family that governs the expression of genes involved in immunity, inflammation, and cell survival (UniProt P19838; Oeckinghaus & Ghosh, 2009). It typically exists in the cytoplasm in an inactive form bound to IκB inhibitory proteins; upon activation by stimuli such as Toll-like receptor ligands or TNF-α, the IκB kinase (IKK) complex phosphorylates IκB, leading to its degradation and the subsequent nuclear translocation of NF-κB (StatPearls, NF-kB Pathway). Once in the nucleus, NF-κB induces the transcription of numerous pro-inflammatory cytokines, including Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1 (IL-1), and Interleukin-6 (IL-6), which serve to amplify and sustain the inflammatory response (Nature Reviews Immunology, Taniguchi & Karin, 2018). Chronic or dysregulated activation of this signaling axis is a primary driver of various pathologies, including rheumatoid arthritis, inflammatory bowel disease, and several types of cancer where it promotes cell proliferation and survival (Baud & Karin, 2009). Therapeutic intervention strategies include the use of proteasome inhibitors like bortezomib to prevent IκB degradation, or monoclonal antibodies such as infliximab and tocilizumab to neutralize the downstream cytokines or their receptors (DrugBank; PubMed). However, because NF-κB is essential for normal host defense and cellular homeostasis, systemic inhibition presents significant therapeutic challenges, most notably a heightened risk of opportunistic infections and impaired tissue repair (NIH, PMC3491448).

Other names

NF-kappaB signaling pathwayNF-kB/cytokine axisPro-inflammatory cascadeNF-kappa-B and cytokines

Inhibition of the IKK complex, proteasome inhibition to prevent IκB degradation, and direct neutralization of downstream cytokines or their receptors (Baud & Karin, 2009; DrugBank; StatPearls).