Toll-like receptor 4 and nuclear factor NF-kappa-B p65 subunit pathway (TLR4 / NF-κB p65 pathway)

Toll-like receptor 4 (TLR4) is a transmembrane pattern recognition receptor that detects bacterial lipopolysaccharide (LPS) and other ligands to initiate innate immune and inflammatory responses by activating intracellular signaling cascades[1][3][5][7]. Downstream of TLR4, the principal pathway involves adapter proteins (e.g., MyD88, TRIF) leading to activation of the IKK complex, subsequent degradation of IκB inhibitors, and nuclear translocation of NF-κB transcription factors, especially the p65 (RELA) subunit. The nuclear factor kappa-B p65 subunit then drives transcription of numerous pro-inflammatory cytokines and survival genes, mediating host defense, but is also implicated in chronic inflammation, cancer, and autoimmune diseases[4][6][8]. Drugs targeting this signaling axis focus on blunting excessive inflammation or inappropriate immune activation. If a single structured target is required, it is preferable to define Toll-like receptor 4 and nuclear factor NF-kappa-B p65 subunit as separate canonical entries, each with their own structured data. The phrase “TLR4 / NF-κB p65 pathway” more accurately refers to a signaling cascade, not a molecular target.

Other names

TLR4-NF-κB p65 signaling cascadeTLR4–NF-κB pathwayTLR4-mediated NF-κB activation

Blockade of TLR4 prevents LPS binding and downstream signaling; Inhibition of NF-κB nuclear translocation or DNA binding; Inhibition of IκB degradation, thus preventing NF-κB activation; Direct inhibition of p65 DNA binding or transcriptional activity.