Lipopolysaccharide-induced cytokine and chemokine pathways

The Lipopolysaccharide-induced cytokine and chemokine pathways (LPS-induced pathways) describe the signaling cascade initiated by the detection of Gram-negative bacterial endotoxins by the innate immune system (Lu et al., 2008). The process begins when LPS is recognized by the Toll-like receptor 4 (TLR4) complex, which requires the co-receptors MD-2 and CD14 for stable binding and activation (Park & Lee, 2013). This interaction triggers two distinct intracellular signaling branches: the MyD88-dependent pathway, which activates the NF-kappaB and MAPK cascades to induce pro-inflammatory cytokines such as TNF-alpha and IL-6, and the TRIF-dependent pathway, which leads to the production of Type I interferons and chemokines like CXCL10 (Matsuura, 2013). While these pathways are vital for clearing infections, their systemic over-activation can lead to lethal conditions such as sepsis, septic shock, and multi-organ failure (Opal, 2010). Therapeutic strategies targeting these pathways include TLR4 antagonists like Eritoran and Resatorvid, as well as agents that neutralize downstream cytokines or inhibit intracellular kinases involved in the signal transduction (Cavaillon, 2018).

Other names

LPS signaling pathwayTLR4 signaling pathwayEndotoxin-induced inflammatory cascadeLPS-TLR4-NF-kappaB axis

Inhibition of the primary receptor (TLR4), neutralization of the LPS ligand, or blockade of downstream signaling mediators and effector cytokines.