The study investigates the role of Toll-like receptor 4 (TLR4) in lipopolysaccharide (LPS)-induced signal transduction. TLR4, a member of the Toll-like receptor family, is identified as the gene necessary for potent responses to LPS in mammals. Using HEK 293 cells transiently transfected with human TLR4 cDNA and an NF-κB-dependent luciferase reporter plasmid, the researchers found that LPS stimulates NF-κB-mediated gene expression in a dose- and time-dependent manner. The LPS antagonist E5531 blocked TLR4-mediated transgene activation in a dose-dependent manner (IC50 ~30 nM). These findings demonstrate that TLR4 is involved in LPS signaling and serves as a cell-surface co-receptor for CD14, leading to LPS-mediated NF-κB activation and subsequent cellular events. The study also highlights the significance of TLR4 as a functional LPS receptor and its potential role in the development of anti-endotoxin agents.The study investigates the role of Toll-like receptor 4 (TLR4) in lipopolysaccharide (LPS)-induced signal transduction. TLR4, a member of the Toll-like receptor family, is identified as the gene necessary for potent responses to LPS in mammals. Using HEK 293 cells transiently transfected with human TLR4 cDNA and an NF-κB-dependent luciferase reporter plasmid, the researchers found that LPS stimulates NF-κB-mediated gene expression in a dose- and time-dependent manner. The LPS antagonist E5531 blocked TLR4-mediated transgene activation in a dose-dependent manner (IC50 ~30 nM). These findings demonstrate that TLR4 is involved in LPS signaling and serves as a cell-surface co-receptor for CD14, leading to LPS-mediated NF-κB activation and subsequent cellular events. The study also highlights the significance of TLR4 as a functional LPS receptor and its potential role in the development of anti-endotoxin agents.