| | |  | | | | Record from Web of Science® | | | | | | |
| Cutting edge: A novel toll/IL-1 receptor Domain containing adapter that preferentially activates the IFN-beta promoter in the toll-like receptor signaling |
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| Author(s): Yamamoto M, Sato S, Mori K, Hoshino K, Takeuchi O, Takeda K, Akira S |
| Source: JOURNAL OF IMMUNOLOGY Volume: 169 Issue: 12 Pages: 6668-6672 Published: DEC 15 2002 |
| Times Cited: 427 References: 20 |
| Abstract: 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-beta (TRIF). As is the case in MyD88 and TIRAP, overexpression of TRIF activated the NF-kappaB-dependent promoter. A dominant-negative form of TRIF inhibited TLR2-, TLR4-, and TLR7-dependent NF-kappaB activation. Furthermore, TRIF, but neither MyD88 nor TIRAP, activated the IFN-beta promoter. Dominant-negative TRIF inhibited TLR3-dependent activation of both the NF-kappaB-dependent and IFN-beta 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Akira, S (reprint author), Osaka Univ, Microbial Dis Res Inst, Dept Host Def, 3-1 Yamada Oka, Osaka 5650871, Japan |
Addresses:
1. Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Osaka 5650871, Japan
2. Japan Sci & Technol Corp, Solut Oriented Res Sci & Technol, Osaka, Japan |
| Publisher: AMER ASSOC IMMUNOLOGISTS, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA |
| Subject Category: Immunology |
| IDS Number: 624MN |
| ISSN: 0022-1767 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |