Abstract
Abstract Signaling pathways from TLRs are mediated by the Toll/IL-1R (TIR) domain-containing adaptor molecules. TNF receptor-associated factor (TRAF) 6 is thought to activate NF-κB and MAPKs downstream of these TIR domain-containing proteins to induce production of inflammatory cytokines. However, the precise role of TRAF6 in signaling from individual TLRs has not been appropriately addressed. We analyzed macrophages from TRAF6-deficient mice and made the following observations. In the absence of TRAF6, 1) ligands for TLR2, TLR5, TLR7, and TLR9 failed to induce activation of NF-κB and MAPKs or production of inflammatory cytokines; 2) TLR4 ligand-induced cytokine production was remarkably reduced and activation of NF-κB and MAPKs was observed, albeit with delayed kinetics; and 3) in contrast with previously reported findings, TLR3 signaling was not affected. These results indicate that TRAF6 is essential for MyD88-dependent signaling but is not required for TIR domain-containing adaptor-inducing IFN-β (TRIF)-dependent signaling.
Keywords
TRIFTLR2Signal transducing adaptor proteinTLR4Cell biologyToll-like receptorSignal transductionTLR3ReceptorTLR7CytokineTLR9ChemistryBiologyImmunologyInnate immune systemBiochemistryGene
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Publication Info
- Year
- 2004
- Type
- article
- Volume
- 173
- Issue
- 5
- Pages
- 2913-2917
- Citations
- 307
- Access
- Closed
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Cite This
Jin Gohda,
Takayuki Matsumura,
Jun‐ichiro Inoue
(2004).
Cutting Edge: TNFR-Associated Factor (TRAF) 6 Is Essential for MyD88-Dependent Pathway but Not Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-β (TRIF)-Dependent Pathway in TLR Signaling.
The Journal of Immunology
, 173
(5)
, 2913-2917.
https://doi.org/10.4049/jimmunol.173.5.2913
Identifiers
- DOI
- 10.4049/jimmunol.173.5.2913