title: Modified 2'-ribose small RNAs function as Toll-like receptor-7/8 antagonists.
abstract: A subset of Toll-like receptors (TLRs) senses microbial nucleic acids in endosomal compartments. Furthermore, under certain conditions TLRs can recognize self-RNAs leading to the induction and/or perpetuation of inflammatory diseases. Recent studies have shown that the incorporation of modified nucleotides into small interfering RNA suppressed unwanted immunostimulation. Interestingly, RNA harboring 2'-ribose modifications, particularly 2'-O-methyl not only evaded immune activation but also suppressed TLR signaling triggered in-trans by immunostimulatory RNAs. This new generation of TLR antagonists may have utility as inhibitors of pathogenic inflammatory reactions mediated by TLR activation. Beyond their structural role, natural modifications in native eukaryotic RNAs may function as endogenous TLR antagonists as well. This chapter describes the characterization of short synthetic small RNAs that suppress immunostimulatory activity in-trans.
authors.affiliation: Department of Immunology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Ullernchausseen 70, Montebello, N-0310, Oslo, Norway, Mouldy.Sioud@rr-research.no.
authors.forename: Mouldy
authors.initials: M
authors.lastname: Sioud
mesh_terms: D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D020869:Gene Expression Profiling; D006801:Humans; D007113:Immunity, Innate; D056747:Immunomodulation; D009000:Monocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D009843:Oligoribonucleotides / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000276:immunology; D012266:Ribose / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D051199:Toll-Like Receptor 7 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D051200:Toll-Like Receptor 8 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology
chemical_list: D005229:Fatty Acids, Monounsaturated; D009843:Oligoribonucleotides; D000644:Quaternary Ammonium Compounds; D034741:RNA, Small Interfering; C495348:TLR7 protein, human; C495349:TLR8 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D014409:Tumor Necrosis Factor-alpha; D012266:Ribose; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane