Results

RDF/XMLNTriplesTurtleShow queryShare
SubjectPredicateObject
http://purl.uniprot.org/citations/20967861http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20967861http://www.w3.org/2000/01/rdf-schema#comment"

Objective

The proinflammatory cytokine interleukin-17A (IL-17A) is produced primarily by the CD4+ T cell subset called Th17 cells, which is involved in host defense, inflammation, and autoimmune disorders. This study was undertaken to investigate the effect of a high-affinity RNA molecule, called an aptamer, against human IL-17A on IL-17A-induced signal transduction in vitro and its anti-autoimmune efficacy in vivo in 2 mouse models of inflammation.

Methods

By screening a large library of nuclease-resistant RNA oligonucleotides, we selected an RNA aptamer, Apt21-2, that binds human and mouse IL-17 and blocks the interaction between IL-17A and its receptor. The inhibition of IL-17A-mediated phosphorylation and marker protein production was analyzed in human and mouse cells. Mice with glucose-6-phosphate isomerase (GPI)-induced rheumatoid arthritis and myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis were used to assess efficacy.

Results

Apt21-2 prevented efficient phosphorylation of the IL-17A signaling factors IκB and JNK and inhibited the production of IL-6 in human and mouse cells. A PEGylated form of Apt21-2 (PEG21-2idT) exhibited a 50% inhibition concentration (IC(50) ) in the range of 1-2 nM and 70-80 nM in human and mouse cells, respectively. When administered immediately after immunization with GPI or MOG, PEG21-2idT inhibited in a dose-dependent manner the development of arthritic or neurologic symptoms. Significantly, PEG21-2idT slowed the progression of arthritis when administered after the onset of GPI-induced arthritis.

Conclusion

Our findings indicate that the chemically processed anti-IL-17A aptamer PEG21-2idT inhibits the actions of IL-17A as well as the development of autoimmunity in 2 mouse models of inflammation. These results offer for the first time an aptamer-based therapeutic approach to the treatment of Th17 cell-mediated autoimmune disorders."xsd:string
http://purl.uniprot.org/citations/20967861http://purl.org/dc/terms/identifier"doi:10.1002/art.30108"xsd:string
http://purl.uniprot.org/citations/20967861http://purl.uniprot.org/core/author"Inoue J."xsd:string
http://purl.uniprot.org/citations/20967861http://purl.uniprot.org/core/author"Nakamura Y."xsd:string
http://purl.uniprot.org/citations/20967861http://purl.uniprot.org/core/author"Adachi H."xsd:string
http://purl.uniprot.org/citations/20967861http://purl.uniprot.org/core/author"Akiyama T."xsd:string
http://purl.uniprot.org/citations/20967861http://purl.uniprot.org/core/author"Ishiguro A."xsd:string
http://purl.uniprot.org/citations/20967861http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/20967861http://purl.uniprot.org/core/name"Arthritis Rheum"xsd:string
http://purl.uniprot.org/citations/20967861http://purl.uniprot.org/core/pages"455-466"xsd:string
http://purl.uniprot.org/citations/20967861http://purl.uniprot.org/core/title"Therapeutic potential of anti-interleukin-17A aptamer: suppression of interleukin-17A signaling and attenuation of autoimmunity in two mouse models."xsd:string
http://purl.uniprot.org/citations/20967861http://purl.uniprot.org/core/volume"63"xsd:string
http://purl.uniprot.org/citations/20967861http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20967861
http://purl.uniprot.org/citations/20967861http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20967861
http://purl.uniprot.org/uniprot/#_Q62386-mappedCitation-20967861http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20967861
http://purl.uniprot.org/uniprot/#_Q544E6-mappedCitation-20967861http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20967861
http://purl.uniprot.org/uniprot/Q544E6http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/20967861
http://purl.uniprot.org/uniprot/Q62386http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/20967861