論文 - 詳細
| RRC ID | 42828 |
|---|---|
| 著者 | Sasai M, Shingai M, Funami K, Yoneyama M, Fujita T, Matsumoto M, Seya T. |
| タイトル | NAK-associated protein 1 participates in both the TLR3 and the cytoplasmic pathways in type I IFN induction. |
| ジャーナル | J Immunol |
| Abstract |
TLR3 and the cytoplasmic helicase family proteins (retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5)) serve as dsRNA pattern-recognition receptors. In response to poly(I:C), a representative of dsRNA, and viral infection, they have been shown to activate the transcription factor IFN regulatory factor (IRF)-3, which in turn induces activation of the IFN-beta promoter. RIG-I/MDA5 recognizes dsRNA in the cytoplasm, whereas TLR3 resides in the cell surface membrane or endosomes to engage in extracytoplasmic recognition of dsRNA. Recent reports suggest that TLR3 induces cellular responses in epithelial cells in response to respiratory syncytial virus (RSV). The modus for TLR3 activation by RSV, however, remains unresolved. By small interference RNA gene-silencing technology and human cell transfectants, we have revealed that knockdown of NAK-associated protein 1 (NAP1) leads to the down-regulation of IFN-beta promoter activation >24 h after poly(I:C) or virus (RSV and vesicular stomatitis virus) treatment. NAP1 is located downstream of the adapter Toll-IL-1R homology domain-containing adapter molecule (TICAM)-1 (Toll/IL-1R domain-containing adapter-inducing IFN-beta) in the TLR3 pathway, but TICAM-1 and TLR3 did not participate in the IRF-3 and IFN-beta promoter activation by RSV infection. Virus-mediated activation of the IFN-beta promoter was largely abrogated by the gene silencing of IFN-beta promoter stimulator-1 (mitochondria antiviral signaling (MAVS), VISA, Cardif), the adapter of the RIG-I/MDA5 dsRNA-recognition proteins. In both the TLR and virus-mediated IFN-inducing pathways, IkappaB kinase-related kinase epsilon and TANK-binding kinase 1 participated in IFN-beta induction. Thus, RSV as well as other viruses induces replication-mediated activation of the IFN-beta promoter, which is intracellularly initiated by the RIG-I/MDA5 but not the TLR3 pathway. Both the cytoplasmic and TLR3-mediated dsRNA recognition pathways converge upon NAP1 for the activation of the IRF-3 and IFN-beta promoter. |
| 巻・号 | 177(12) |
| ページ | 8676-83 |
| 公開日 | 2006-12-15 |
| DOI | 10.4049/jimmunol.177.12.8676 |
| PII | 177/12/8676 |
| PMID | 17142768 |
| MeSH | Cytoplasm / metabolism Gene Expression Regulation / drug effects Gene Expression Regulation / immunology* HeLa Cells Humans Interferon Regulatory Factor-3 / metabolism* Interferon Type I / genetics* Interferon-beta / genetics Promoter Regions, Genetic Protein Serine-Threonine Kinases / metabolism* RNA, Double-Stranded / pharmacology Toll-Like Receptor 3 / metabolism* Viruses / genetics |
| IF | 4.886 |
| 引用数 | 110 |
| WOS 分野 | IMMUNOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Wikipedia |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293(RCB1637) |