| RRC ID |
54463
|
| 著者 |
Matsumoto M, Kikkawa S, Kohase M, Miyake K, Seya T.
|
| タイトル |
Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
A monoclonal antibody (mAb) against human Toll-like receptor (TLR) 3 was established and its effect on TLR3-mediated responses was tested using human fibroblast cell lines expressing TLR3 on the cell surface. Fibroblasts are known to produce IFN-beta upon viral infection or treatment with double-stranded RNA (dsRNA) through distinct signaling pathways. Here, we show the mAb to TLR3 suppressed poly(I):poly(C)-mediated IFN-beta production by human fibroblasts naturally expressing TLR3 on their surface. By reporter gene assay using HEK293 cells transfected with a human TLR3 expression vector, TLR3 recognized dsRNA to activate NF-kappaB and the IFN-beta promoter. TLR3 signaling was not elicited by either single-stranded RNA (ssRNA) or dsDNA. Thus, specific recognition of dsRNA by extracellular TLR3 is essential for induction of type I IFN: the interassociation between dsRNA and TLR3, regardless of direct or indirect binding, should be disrupted by mAb being attached to TLR3. The mAb against TLR3 reported herein may serve as a regulator for virus-mediated immune response via an alternative pathway involving the dsRNA-TLR3 recognition which might occur on host cells.
|
| 巻・号 |
293(5)
|
| ページ |
1364-9
|
| 公開日 |
2002-5-24
|
| DOI |
10.1016/S0006-291X(02)00380-7
|
| PII |
S0006-291X(02)00380-7
|
| PMID |
12054664
|
| MeSH |
Animals
Antibodies, Monoclonal / metabolism*
Cell Line
Cell Membrane / metabolism
DNA, Complementary / metabolism
Dose-Response Relationship, Drug
Drosophila Proteins*
Fibroblasts / metabolism
Flow Cytometry
Genes, Reporter
Genetic Vectors
Humans
Interferon-beta / metabolism
Luciferases / metabolism
Lung / metabolism
Membrane Glycoproteins / chemistry
Membrane Glycoproteins / immunology*
Mice
Mice, Inbred BALB C
NF-kappa B / metabolism
Promoter Regions, Genetic
Protein Binding
RNA / metabolism*
RNA, Double-Stranded / metabolism
Receptors, Cell Surface / chemistry
Receptors, Cell Surface / immunology*
Recombinant Proteins / metabolism
Signal Transduction
Toll-Like Receptor 3
Toll-Like Receptors
Transfection
|
| IF |
2.985
|
| 引用数 |
340
|
| リソース情報 |
| 遺伝子材料 |
human TLR3 expression vector (RDB16909)
human TLR3-CFlag expression vector (RDB16911) |
| ヒト・動物細胞 |
MRC-5 |
