RRC ID 54463
Author Matsumoto M, Kikkawa S, Kohase M, Miyake K, Seya T.
Title Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling.
Journal 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.
Volume 293(5)
Pages 1364-9
Published 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
Times Cited 340
Altmetric score
オルトメトリクス指標項目
The most frequently cited source Patent(IFI CLAIMS)
Total number of mentions 52
Altmetric score changes over past 6months 0.0
Resource
DNA material human TLR3 expression vector (RDB16909) human TLR3-CFlag expression vector (RDB16911)
Human and Animal Cells MRC-5