Reference - Detail
| RRC ID | 1957 |
|---|---|
| Author | Okahira S, Nishikawa F, Nishikawa S, Akazawa T, Seya T, Matsumoto M. |
| Title | Interferon-beta induction through toll-like receptor 3 depends on double-stranded RNA structure. |
| Journal | DNA Cell Biol |
| Abstract |
Type I interferons (IFN-alpha/beta) play an essential role in both innate and adaptive antiviral immune responses. IFN- beta is produced by fibroblasts and myeloid dendritic cells (DCs) upon viral infection or in response to doublestranded RNA (dsRNA). Several intracellular molecules having a dsRNA-binding motif such as dsRNA-dependent protein kinase recognize dsRNA in a sequence-independent manner and induce antiviral innate responses. Toll-like receptor (TLR) 3, a member of TLR family proteins, recognizes extracellular dsRNA and activates NF- kappaB and the IFN-beta promoter leading to the induction of IFN-beta production. Here we analyzed the dsRNA structure capable of inducing TLR3-mediated IFN-beta production using various synthetic RNA duplexes. In contrast to the recognition of dsRNA by intracellular molecules, TLR3 preferentially recognizes polyriboinocinic:polyribocytidylic acid (poly(I:C)) rather than synthetic virus-derived dsRNAs. 2'-O-methyl or 2'-fluoro modification of cytidylic acid abolished the IFN-beta-inducing ability of the poly(I:C) duplex, and these modified dsRNAs inhibited poly(I:C)-induced TLR3-mediated IFN-beta production by fibroblasts and DCs. In addition, poly(dI:dC), a non-IFN inducer, also blocked poly(I:C)-induced IFN-beta induction. Since TLR3 is localized in the intracellular compartment of DCs where signaling occurs, modified dsRNAs may compete with poly(I:C) for binding to the cell-surface receptor that transfers dsRNA into TLR3-enriched vesicles. Thus, TLR3 recognizes a unique dsRNA structure that largely differs from those recognized by other dsRNA-binding proteins. |
| Volume | 24(10) |
| Pages | 614-23 |
| Published | 2005-10-1 |
| DOI | 10.1089/dna.2005.24.614 |
| PMID | 16225392 |
| MeSH | Cells, Cultured Cytokines / metabolism Fibroblasts / cytology Fibroblasts / metabolism Flow Cytometry Humans Interferon-beta / genetics Interferon-beta / metabolism* Interferon-beta / pharmacology Kidney / metabolism Lung / metabolism Membrane Glycoproteins / metabolism* Poly I-C / pharmacology* RNA, Double-Stranded / chemistry* RNA, Double-Stranded / metabolism Receptors, Cell Surface / metabolism* Ribose / chemistry* Toll-Like Receptor 3 Toll-Like Receptors |
| IF | 3.314 |
| Times Cited | 60 |
| WOS Category | GENETICS & HEREDITY BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| Altmetric score |
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 9 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | MRC-5 |