| Dual or Triple Activation of TLR7, TLR8, and/or TLR9 by Single-Stranded Oligoribonucleotides. | |
| | |
MedLine Citation:
|
PMID: 22196370 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
The toll-like receptors (TLRs) 7, 8, and 9 stimulate innate immune responses upon recognizing pathogen nucleic acids. Certain GU- or AU-rich RNA sequences were described to differentiate between human TLR7- and TLR8-mediated immune effects. Those single-stranded RNA molecules require endosomal delivery for stabilization against ribonucleases. We have discovered RNA sequences that preferentially activate TLR7, form higher ordered structures, and do not require specific cellular delivery. In addition, a dual activation of TLR8 and TLR9 without affecting TLR7 can be achieved by chimeric molecules consisting of GU-rich RNA and Cytosin (C) phosphordiester or phosphorthioat (p) guanine (CpG) motif DNA sequences. Such chimeras stimulate TLR9-mediated type I interferon (IFN) and TLR8-depending proinflammatory cytokine and chemokine production upon primary human cell activation. However, an RNA-dependent TLR7 IFN-α cytokine release is suppressed by the phosphorothioate DNA sequence contained in the chimeric molecule. To convert the immune response of a single-stranded RNA from TLR7/8 to TLR9, a simple chemical modification at the 5' end proves to be sufficient. Such 8-oxo-2'-deoxy-guanosine or 8-bromo-2'-deoxy-guanosine modifications of the first guanosine in GU-rich single-stranded RNAs convert the immune response to include TLR9 activation and demonstrate strong additive effects for type I IFN immune responses in human primary cells. |
| | |
Authors:
|
Alexandra Forsbach; Ulrike Samulowitz; Kirsten Völp; Hans-Peter Hofmann; Bernhard Noll; Sybille Tluk; Claudia Schmitz; Tanja Wader; Christian Müller; Anja Podszuweit; Angela Lohner; Rainer Curdt; Eugen Uhlmann; Jörg Vollmer |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Nucleic acid therapeutics Volume: 21 ISSN: 2159-3345 ISO Abbreviation: Nucleic Acid Ther Publication Date: 2011 Dec |
Date Detail:
|
Created Date: 2011-12-26 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 101562758 Medline TA: Nucleic Acid Ther Country: United States |
Other Details:
|
Languages: eng Pagination: 423-36 Citation Subset: IM |
Affiliation:
|
Pfizer Oligonucleotides Therapeutics Unit, Coley Pharmaceutical GmbH , Düsseldorf, Germany . |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Structure of the O-polysaccharide chain of the lipopolysaccharide of Psychrobacter muricolla 2pS(T) ...
Next Document: Rehearsal dynamics in elementary school children.