Linked Life Data

20488664

Source:http://linkedlifedata.com/resource/pubmed/id/20488664

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-8-23
pubmed:abstractText
Several lines of evidence link Interferons (IFNs) with autoimmune disorders. Autoantibodies against the Interferon-inducible IFI16 protein, a member of the HIN-200 family constitutively expressed in endothelial cells and keratinocytes, have been identified in patients affected by autoimmune diseases including Systemic Lupus Erythematosus (SLE), Sjogren Syndrome (SjS), and Scleroderma (SSc). These findings point to a role for IFI16 in the etiopathogenesis of autoimmune diseases, but the exact mechanisms involved in the development of autoimmunity remain obscure. In this study, we report for the first time that endothelial cells overexpressing IFI16 undergo apoptosis via the activation of caspase 2 and caspase 3, and that a positive feedback loop appears to link these two caspases. The relevance of IFI16-mediated apoptosis is highlighted by the observation that IFI16 knock down by RNA interference in endothelial cells inhibits the activation of both caspase 2 and caspase 3 by IFN-beta priming and synthetic double-stranded RNA treatment. Expression of a dominant-negative mutant of IKK2 kinase or treatment with AS602868, an inhibitor of IKK2 activity, results in a strong reduction of NF-kB activation along with absence of caspase 2 and caspase 3 activation and apoptosis induction. Collectively, our findings provide new insights into the role of IFI16 in the pathogenesis of autoimmune diseases by demonstrating that in addition to the stimulation of pro-inflammatory molecules, IFI16 also leads to apoptosis in endothelial cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/AS602868, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 2, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3, http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase, http://linkedlifedata.com/resource/pubmed/chemical/IFI16 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Interferon-beta, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Double-Stranded, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1095-9157
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
114-23
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
The proapoptotic activity of the Interferon-inducible gene IFI16 provides new insights into its etiopathogenetic role in autoimmunity.
pubmed:affiliation
Department of Public Health and Microbiology, University of Turin, Via Santena 9, Turin, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't