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Enterovirus-induced...
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Ylipaasto, P.Intestinal Viruses Unit, National Intestinal Viruses Unit, National Institute for Health and Welfare (THL), Helsinki, Finland
(författare)
Enterovirus-induced gene expression profile is critical for human pancreatic islet destruction
- Artikel/kapitelEngelska2012
Förlag, utgivningsår, omfång ...
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2012-09-16
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Springer Science and Business Media LLC,2012
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-184885
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-184885URI
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https://doi.org/10.1007/s00125-012-2713-zDOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-63673URI
Kompletterande språkuppgifter
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Språk:engelska
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Sammanfattning på:engelska
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Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Funding agencies:Juvenile Diabetes Research Foundation (USA)European Union EP7-HEALTH-2007 DIA-PREPP N202013Academy of FinlandPaivikki and Sakari Sohlberg FoundationFinnish Diabetes FoundationMaud Kuistila Memorial Foundation
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Aims/hypothesis Virally induced inflammatory responses, beta cell destruction and release of beta cell autoantigens may lead to autoimmune reactions culminating in type 1 diabetes. Therefore, viral capability to induce beta cell death and the nature of virus-induced immune responses are among key determinants of diabetogenic viruses. We hypothesised that enterovirus infection induces a specific gene expression pattern that results in islet destruction and that such a host response pattern is not shared among all enterovirus infections but varies between virus strains. Methods The changes in global gene expression and secreted cytokine profiles induced by lytic or benign enterovirus infections were studied in primary human pancreatic islet using DNA microarrays and viral strains either isolated at the clinical onset of type 1 diabetes or capable of causing a diabetes-like condition in mice. Results The expression of pro-inflammatory cytokine genes (IL-1-a, IL-1-β and TNF-a) that also mediate cytokineinduced beta cell dysfunction correlated with the lytic potential of a virus. Temporally increasing gene expression levels of double-stranded RNArecognition receptors, antiviral molecules, cytokines and chemokines were detected for all studied virus strains. Lytic coxsackievirus B5 (CBV-5)-DS infection also downregulated genes involved in glycolysis and insulin secretion. Conclusions/interpretation The results suggest a distinct, virusstrain- specific, gene expression pattern leading to pancreatic islet destruction and pro-inflammatory effects after enterovirus infection. However, neither viral replication nor cytotoxic cytokine production alone are sufficient to induce necrotic cell death. More likely the combined effect of these and possibly cellular energy depletion lie behind the enterovirus-induced necrosis of islets.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Smura, T.Intestinal Viruses Unit, National Institute for Health and Welfare (THL), Helsinki, Finland
(författare)
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Gopalacharyulu, P.VTT Technical Research Center of Finland, Espoo, Finland
(författare)
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Paananen, A.Intestinal Viruses Unit, National Institute for Health and Welfare (THL), Helsinki, Finland
(författare)
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Seppänen-Laakso, T.VTT Technical Research Center of Finland, Espoo, Finland
(författare)
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Kaijalainen, S.Intestinal Viruses Unit, National Institute for Health and Welfare (THL), Helsinki, Finland
(författare)
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Ahlfors, H.Division of Molecular Immunology, MRC National Institute for Medical Research, London, United Kingdom; Centre for Biotechnology, University of Turku, Turku, Finland
(författare)
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Korsgren, OlleUppsala universitet,Klinisk immunologi,korsgren,Division of Clinical Immunology, Department of Oncology, Radiology, and Clinical Immunology, Uppsala University, Uppsala, Sweden(Swepub:uu)ollekors
(författare)
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Lakey, J. R. T.Department of Surgery, University of California, Irvine CA, United States
(författare)
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Lahesmaa, R.Centre for Biotechnology, University of Turku, Turku, Finland
(författare)
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Piemonti, L.Diabetes Research Institute (HSR-DRI), San Raffaele Scientific Institute, Milan, Italy
(författare)
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Oresic, Matej,1967-Örebro universitet,Institutionen för medicinska vetenskaper,Intestinal Viruses Unit, National Institute for Health and Welfare (THL), Helsinki, Finland(Swepub:oru)moc
(författare)
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Galama, J.Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands
(författare)
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Roivainen, M.Intestinal Viruses Unit, National Institute for Health and Welfare (THL), Helsinki, Finland
(författare)
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Intestinal Viruses Unit, National Intestinal Viruses Unit, National Institute for Health and Welfare (THL), Helsinki, FinlandIntestinal Viruses Unit, National Institute for Health and Welfare (THL), Helsinki, Finland
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Diabetologia: Springer Science and Business Media LLC55:12, s. 3273-32830012-186X1432-0428
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- Av författaren/redakt...
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Ylipaasto, P.
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Smura, T.
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Gopalacharyulu, ...
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Paananen, A.
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Seppänen-Laakso, ...
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Kaijalainen, S.
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visa fler...
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Ahlfors, H.
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Korsgren, Olle
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Lakey, J. R. T.
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Lahesmaa, R.
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Piemonti, L.
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Oresic, Matej, 1 ...
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Galama, J.
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Roivainen, M.
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Gastroenterologi
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Diabetologia
- Av lärosätet
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Uppsala universitet
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Örebro universitet