Toll-like Receptor-4 Mediates Lipopolysaccharide-induced Signal Transduction
TLR4 is a member of the recently identified Toll-like receptor family of proteins and has been putatively identified as Lps, the gene necessary for potent responses to lipopolysaccharide in mammals. In order to determine whether TLR4 is involved in lipopolysaccharide-induced activation of the nuclea...
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Published in | The Journal of biological chemistry Vol. 274; no. 16; pp. 10689 - 10692 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
16.04.1999
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Subjects | |
Online Access | Get full text |
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Summary: | TLR4 is a member of the recently identified Toll-like receptor family of proteins and has been putatively identified as Lps, the gene necessary for potent responses to lipopolysaccharide in mammals. In order to determine whether TLR4 is involved
in lipopolysaccharide-induced activation of the nuclear factor-κB (NF-κB) pathway, HEK 293 cells were transiently transfected
with human TLR4 cDNA and an NF-κB-dependent luciferase reporter plasmid followed by stimulation with lipopolysaccharide/CD14
complexes. The results demonstrate that lipopolysaccharide stimulates NF-κB-mediated gene expression in cells transfected
with the TLR4 gene in a dose- and time-dependent fashion. Furthermore, E5531, a lipopolysaccharide antagonist, blocked TLR4-mediated
transgene activation in a dose-dependent manner (IC 50 â¼30 n m ). These data demonstrate that TLR4 is involved in lipopolysaccharide signaling and serves as a cell-surface co-receptor for
CD14, leading to lipopolysaccharide-mediated NF-κB activation and subsequent cellular events. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.274.16.10689 |