mRNA Is an Endogenous Ligand for Toll-like Receptor 3*

@article{Karik2004mRNAIA,
  title={mRNA Is an Endogenous Ligand for Toll-like Receptor 3*},
  author={Katalin Karik{\'o} and Houping Ni and John Capodici and Marc S. Lamphier and Drew Weissman},
  journal={Journal of Biological Chemistry},
  year={2004},
  volume={279},
  pages={12542 - 12550}
}
Toll-like receptors (TLRs) are the basic signaling receptors of the innate immune system. They are activated by molecules associated with pathogens or injured host cells and tissue. TLR3 has been shown to respond to double stranded (ds) RNA, a replication intermediary for many viruses. Here we present evidence that heterologous RNA released from or associated with necrotic cells or generated by in vitro transcription also stimulates TLR3 and induces immune activation. To assess RNA-mediated… Expand
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TLDR
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References

SHOWING 1-10 OF 60 REFERENCES
Toll-Like Receptor 3 Mediates a More Potent Antiviral Response Than Toll-Like Receptor 41
TLDR
It is argued that, despite both TLR3 and TLR4 being able to use IFN-β to activate/enhance antiviral gene expression,TLR3 uses multiple mechanisms to enhance and sustain the antiviral response more strongly thanTLR4. Expand
Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling.
TLDR
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. Expand
Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
TLDR
It is shown that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-κB and the production of type I interferons (IFNs). Expand
Regulation of Toll-Like Receptors in Human Monocytes and Dendritic Cells1
TLDR
TLRs are expressed in iDC and are involved in responses to at least one pathogen-derived substance, LPS, and its extremely low surface expression implies that it is a very efficient signal transducer in i DC. Expand
Cellular Events Mediated by Lipopolysaccharide-stimulated Toll-like Receptor 4
TLDR
It is demonstrated that expression of both TLR4 and MD-2 is required for LPS to activate or augment the MAP kinase pathways, Elk-1 stimulation, and IL-8 generation. Expand
TICAM-1, an adaptor molecule that participates in Toll-like receptor 3–mediated interferon-β induction
TLDR
This work has identified an alternative adaptor, designated Toll-interleukin 1 receptor domain (TIR)-containing adaptor molecule (TICAM)-1, that can physically bind the TIR domain of TLR3 and activate the IFN-β promoter in response to poly(I):poly(C). Expand
Double-stranded RNA Signaling by Toll-like Receptor 3 Requires Specific Tyrosine Residues in Its Cytoplasmic Domain*
TLDR
It is reported that induction of the 561 mRNA by exogenous dsRNA is mediated by Toll-like receptor 3 (TLR3), and it requires no new protein synthesis. Expand
TLR4, but not TLR2, mediates IFN-β–induced STAT1α/β-dependent gene expression in macrophages
Toll-like receptor 2 (TLR2) agonists induce a subset of TLR4-inducible proinflammatory genes, which suggests the use of differential signaling pathways. Murine macrophages stimulated with the TLR4Expand
TIRAP: an adapter molecule in the Toll signaling pathway
TLDR
A Toll–interleukin 1 receptor–containing adapter protein (TIRAP) is identified and characterized and it is shown that it controls activation of MyD88-independent signaling pathways downstream of TLR4. Expand
IFNs activate toll-like receptor gene expression in viral infections
TLDR
The data suggest a novel role for IFNs in the activation of innate immunity, and TLR1–9 mRNA expression in human primary macrophages infected with influenza A and Sendai viruses is analyzed. Expand
...
1
2
3
4
5
...