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http://purl.uniprot.org/citations/18223009http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18223009http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Viral infections contribute to the pathogenesis of type 1 diabetes. Viruses, or viral products such as double-stranded RNA (dsRNA), affect pancreatic beta-cell survival and trigger autoimmunity by unknown mechanisms. We presently investigated the mediators and downstream effectors of dsRNA-induced beta-cell death.

Research design and methods

Primary rat beta-cells and islet cells from wild-type, toll-like receptor (TLR) 3, type I interferon receptor (IFNAR1), or interferon regulatory factor (IRF)-3 knockout mice were exposed to external dsRNA (external polyinosinic-polycytidylic acid [PICex]) or were transfected with dsRNA ([PICin]).

Results

TLR3 signaling mediated PICex-induced nuclear factor-kappaB (NF-kappaB) and IRF-3 activation and beta-cell apoptosis. PICin activated NF-kappaB and IRF-3 in a TLR3-independent manner, induced eukaryotic initiation factor 2 alpha phosphorylation, and triggered a massive production of interferon (IFN)-beta. This contributed to beta-cell death, as islet cells from IFNAR1(-/-) or IRF-3(-/-) mice were protected against PICin-induced apoptosis.

Conclusions

PICex and PICin trigger beta-cell apoptosis via the TLR3 pathway or IRF-3 signaling, respectively. Execution of PICin-mediated apoptosis depends on autocrine effects of type I IFNs."xsd:string
http://purl.uniprot.org/citations/18223009http://purl.org/dc/terms/identifier"doi:10.2337/db07-0844"xsd:string
http://purl.uniprot.org/citations/18223009http://purl.uniprot.org/core/author"Garcia M."xsd:string
http://purl.uniprot.org/citations/18223009http://purl.uniprot.org/core/author"Flamez D."xsd:string
http://purl.uniprot.org/citations/18223009http://purl.uniprot.org/core/author"Mathieu C."xsd:string
http://purl.uniprot.org/citations/18223009http://purl.uniprot.org/core/author"Alexopoulou L."xsd:string
http://purl.uniprot.org/citations/18223009http://purl.uniprot.org/core/author"Libert C."xsd:string
http://purl.uniprot.org/citations/18223009http://purl.uniprot.org/core/author"Goldman M."xsd:string
http://purl.uniprot.org/citations/18223009http://purl.uniprot.org/core/author"Eizirik D.L."xsd:string
http://purl.uniprot.org/citations/18223009http://purl.uniprot.org/core/author"Dogusan Z."xsd:string
http://purl.uniprot.org/citations/18223009http://purl.uniprot.org/core/author"Rasschaert J."xsd:string
http://purl.uniprot.org/citations/18223009http://purl.uniprot.org/core/author"Gysemans C."xsd:string
http://purl.uniprot.org/citations/18223009http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18223009http://purl.uniprot.org/core/name"Diabetes"xsd:string
http://purl.uniprot.org/citations/18223009http://purl.uniprot.org/core/pages"1236-1245"xsd:string
http://purl.uniprot.org/citations/18223009http://purl.uniprot.org/core/title"Double-stranded RNA induces pancreatic beta-cell apoptosis by activation of the toll-like receptor 3 and interferon regulatory factor 3 pathways."xsd:string
http://purl.uniprot.org/citations/18223009http://purl.uniprot.org/core/volume"57"xsd:string
http://purl.uniprot.org/citations/18223009http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/18223009
http://purl.uniprot.org/citations/18223009http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/18223009
http://purl.uniprot.org/uniprot/P70499#attribution-00CD1B9511CB701A5D9B47DDDFCAEC26http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/18223009
http://purl.uniprot.org/uniprot/A6JAV4#attribution-00CD1B9511CB701A5D9B47DDDFCAEC26http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/18223009
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http://purl.uniprot.org/uniprot/F7EXX5#attribution-00CD1B9511CB701A5D9B47DDDFCAEC26http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/18223009
http://purl.uniprot.org/uniprot/Q5XIB0#attribution-00CD1B9511CB701A5D9B47DDDFCAEC26http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/18223009
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