| RRC ID |
1957
|
| 著者 |
Okahira S, Nishikawa F, Nishikawa S, Akazawa T, Seya T, Matsumoto M.
|
| タイトル |
Interferon-beta induction through toll-like receptor 3 depends on double-stranded RNA structure.
|
| ジャーナル |
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.
|
| 巻・号 |
24(10)
|
| ページ |
614-23
|
| 公開日 |
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
|
| 引用数 |
60
|
|
WOS 分野
|
GENETICS & HEREDITY
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
MRC-5 |
