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Cutting Edge: A Novel Toll/IL-1 Receptor Domain-Containing Adapter That Preferentially Activates the IFN-β Promoter in the Toll-Like Receptor Signaling
Open accessAbstract
MyD88 is a Toll/IL-1 receptor (TIR) domain-containing adapter common to signaling pathways via Toll-like receptor (TLR) family. However, accumulating evidence demonstrates the existence of a MyD88-independent pathway, which may explain unique biological responses of individual TLRs, particularly TLR3 and TLR4. TIR domain-containing adapter protein (TIRAP)/MyD88 adapter-like, a second adapter harboring the TIR domain, is essential for MyD88-dependent TLR2 and TLR4 signaling pathways, but not for MyD88-independent pathways. Here, we identified a novel TIR domain-containing molecule, named TIR domain-containing adapter inducing IFN-β (TRIF). As is the case in MyD88 and TIRAP, overexpression of TRIF activated the NF-κB-dependent promoter. A dominant-negative form of TRIF inhibited TLR2-, TLR4-, and TLR7-dependent NF-κB activation. Furthermore, TRIF, but neither MyD88 nor TIRAP, activated the IFN-β promoter. Dominant-negative TRIF inhibited TLR3-dependent activation of both the NF-κB-dependent and IFN-β promoters. TRIF associated with TLR3 and IFN regulatory factor 3. These findings suggest that TRIF is involved in the TLR signaling, particularly in the MyD88-independent pathway.
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Metadata
- Authors
- Yamamoto, M., Sato, S., Mori, K., Hoshino, K., Takeuchi, O., Takeda, K., & Akira, S.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2002-12
- Volume
- 169
- Issue
- 12
- Pages
- 6668-6672
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2148387062
- Cited by
- 1,227
- References
- 3
- FWCI
- 28.71
- Type
- journal article
- Language
- en
- Open access
- bronze
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