Lipopolysaccharide–Toll-like receptor 4–Nuclear factor-kappa B signaling pathway (LPS–TLR4–NF-κB axis)

The Lipopolysaccharide–Toll-like receptor 4–Nuclear factor-kappa B (LPS–TLR4–NF-κB) axis is a central signaling cascade in the innate immune system that mediates the inflammatory response to Gram-negative bacteria. Lipopolysaccharide (LPS), a component of the bacterial outer membrane, is recognized by Toll-like receptor 4 (TLR4) in complex with MD-2 and CD14, triggering a downstream signaling cascade. This activation typically proceeds through MyD88-dependent or TRIF-dependent pathways, ultimately leading to the phosphorylation and degradation of IκB proteins. The subsequent release and nuclear translocation of the transcription factor NF-κB induce the expression of pro-inflammatory cytokines, chemokines, and interferons. Dysregulation of this axis is a primary driver of clinical conditions such as septic shock, chronic inflammatory diseases, and certain cancers where persistent inflammation promotes tumor progression. Therapeutic strategies targeting this axis include TLR4 antagonists, LPS-sequestering agents, and small molecule inhibitors of the NF-κB complex to mitigate excessive inflammatory damage.

Other names

TLR4/NF-κB signaling pathwayLPS-induced TLR4 signalingLipopolysaccharide-mediated NF-kappaB activationTLR4-MyD88-NF-kappaB axis

TLR4 antagonism, LPS neutralization, MyD88 inhibition, IKK inhibition, NF-κB nuclear translocation inhibition