2008
DOI: 10.1128/mcb.00308-08
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Single-Stranded Oligonucleotides Can Inhibit Cytokine Production Induced by Human Toll-Like Receptor 3

Abstract: Toll-like receptor 3 (TLR3) can signal the production of a suite of cytokines and chemokines in response to double-stranded RNA (dsRNA) ligands or the dsRNA mimic poly(I-C). Using a human embryonic kidney 293T cell line to express human TLR3, we determined that poly(I-C)-induced signal could be significantly inhibited by single-stranded DNAs (ssDNAs), but not ssRNA or dsDNA. The ssDNA molecules that down-modulated TLR3 signaling did not affect TLR4 and do not require the hypomethylated CpG motif found in TLR9 … Show more

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Cited by 33 publications
(52 citation statements)
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References 40 publications
(62 reference statements)
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“…1B except css27, consistent with reports that ssRNA require a 5Ј-triphosphate to act as an RIG-I agonist (25,26). Double-stranded RNAs dsR27, pIC25, pIC115, and poly(I:C) were able to activate RIG-I signaling in the absence of the 5Ј-triphosphates from 6-to 13-fold (Fig.…”
Section: Resultssupporting
confidence: 88%
See 2 more Smart Citations
“…1B except css27, consistent with reports that ssRNA require a 5Ј-triphosphate to act as an RIG-I agonist (25,26). Double-stranded RNAs dsR27, pIC25, pIC115, and poly(I:C) were able to activate RIG-I signaling in the absence of the 5Ј-triphosphates from 6-to 13-fold (Fig.…”
Section: Resultssupporting
confidence: 88%
“…Modified ODNs with phosphorothioate backbones can bind to the ectodomain of TLR3 and inhibit signaling (26). We wanted to assess whether ODNs such as 2006 can affect RIG-I activity in the cellbased assay (Fig.…”
Section: Antagonists Of Rig-i Signaling-mentioning
confidence: 99%
See 1 more Smart Citation
“…B, shown is the effects of siRNA to Unc93b1 on TLR4-dependent signal transduction. Cells were transfected to express TLR4 and its co-activators and induced with 1 g/ml lipopolysaccharide as described previously (47). The firefly luciferase reporter is driven by the NF-B promoter and normalized to the Renilla luciferase driven by the thymidine kinase promoter.…”
Section: Resultsmentioning
confidence: 99%
“…Further evidence for a role for the endosomal TLRs in CIA has also come from studies with short DNA oligonucleotides (ODNs). These act as Immunoregulatory Sequences (IRS) and inhibit endosomal TLR activity (Barrat et al, 2005;Ranjith-Kumar et al, 2008;Lenert, 2010). Prophylactic administration of ODNs in CIA and CpG-induced arthritis has been shown to abrogate disease progression (Zeuner et al, 2002;Dong et al, 2004).…”
Section: Targeting Tlrs As a Therapy In Ramentioning
confidence: 99%