Tumor necrosis factor–Nuclear factor-kappa B signaling pathway (TNF–NF-κB axis)

The Tumor necrosis factor–Nuclear factor-kappa B (TNF–NF-κB) inflammatory axis is a central signaling cascade that governs the body's response to inflammation, infection, and cellular stress (PubMed: 12496477). The process is initiated when the cytokine TNF-α binds to its cell surface receptors, TNFR1 or TNFR2, leading to the recruitment of adapter proteins and the activation of the IκB kinase (IKK) complex (UniProt: P01375, P19438). This activation results in the phosphorylation and subsequent proteasomal degradation of IκB inhibitory proteins, which normally sequester NF-κB in the cytoplasm (PubMed: 10891884). Once released, NF-κB dimers translocate to the nucleus to induce the transcription of a wide array of pro-inflammatory genes, including cytokines, chemokines, and adhesion molecules (PubMed: 16751770). Chronic overactivation of this axis is a primary driver of autoimmune and inflammatory disorders such as rheumatoid arthritis and Crohn's disease, as well as contributing to tumor progression and chemoresistance in cancer (PubMed: 11046032). Consequently, therapeutic intervention often focuses on neutralizing TNF-α with monoclonal antibodies or decoy receptors to dampen the inflammatory cascade (PubChem: CID 135315457).

Other names

TNF-alpha/NF-kappaB pathwayTNF-mediated NF-kappaB signalingTNFR-NF-kappaB axisTumor necrosis factor-mediated NF-kappaB activation

Neutralization of soluble and membrane-bound TNF-alpha to prevent receptor binding, or inhibition of downstream signaling components like the IKK complex or proteasome to prevent NF-kappaB nuclear translocation.