Cytokines interleukin-1beta and tumor necrosis factor-alpha regulate different transcriptional and alternative splicing networks in primary beta-cells.

Diabetes
F OrtisD L Eizirik

Abstract

Cytokines contribute to pancreatic beta-cell death in type 1 diabetes. This effect is mediated by complex gene networks that remain to be characterized. We presently utilized array analysis to define the global expression pattern of genes, including spliced variants, modified by the cytokines interleukin (IL)-1beta + interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha + IFN-gamma in primary rat beta-cells. Fluorescence-activated cell sorter-purified rat beta-cells were exposed to IL-1beta + IFN-gamma or TNF-alpha + IFN-gamma for 6 or 24 h, and global gene expression was analyzed by microarray. Key results were confirmed by RT-PCR, and small-interfering RNAs were used to investigate the mechanistic role of novel and relevant transcription factors identified by pathway analysis. RESULTS Nearly 16,000 transcripts were detected as present in beta-cells, with temporal differences in the number of genes modulated by IL-1beta + IFNgamma or TNF-alpha + IFN-gamma. These cytokine combinations induced differential expression of inflammatory response genes, which is related to differential induction of IFN regulatory factor-7. Both treatments decreased the expression of genes involved in the maintenance of beta-cell phenotype and ...Continue Reading

References

Feb 4, 1999·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·J H NielsenN Billestrup
Jan 17, 2002·Diabetologia·D L Eizirik, T Mandrup-Poulsen
Sep 6, 2002·Biochemical Pharmacology·Jean-Pascal PiretCarine Michiels
Jul 15, 2006·Cell·Benjamin J Blencowe
Aug 5, 2006·Molecular Pharmacology·Qingdong Ke, Max Costa
Apr 4, 2007·Annals of the New York Academy of Sciences·Marco SgarbantiAngela Battistini
Jul 20, 2007·Immunology and Cell Biology·Ayelet KaminitzNadir Askenasy
Dec 1, 2007·Endocrine Reviews·Décio L EizirikMiriam Cnop
Apr 26, 2008·Endocrine Reviews·Stephanie T PageWilliam J Bremner
May 17, 2008·Biochemical Society Transactions·Decio L EizirikFernanda Ortis
Aug 30, 2008·Nature·Qiao ZhouDouglas A Melton
Nov 4, 2008·Nature·Eric T WangChristopher B Burge
Dec 9, 2008·The Biochemical Journal·Jennifer C Long, Javier F Caceres
Jan 31, 2009·Proceedings of the National Academy of Sciences of the United States of America·Kathleen A O'HaganBernard B Allan
Mar 7, 2009·Nature Medicine·Fiona M Gribble
Mar 27, 2009·Apoptosis : an International Journal on Programmed Cell Death·Helen E ThomasThomas W Kay
Apr 1, 2009·Experimental Cell Research·Nathalie Dehne, Bernhard Brüne
Apr 9, 2009·Nature Reviews. Endocrinology·Décio L EizirikFernanda Ortis
May 1, 2009·Diabetes/metabolism Research and Reviews·Linda M S Pickersgill, Thomas R Mandrup-Poulsen
Jun 17, 2009·Nucleic Acids Research·Dimos GaidatzisMichael B Stadler
Jul 11, 2009·Journal of Clinical Rheumatology : Practical Reports on Rheumatic & Musculoskeletal Diseases·Rodney S DanielMarcy B Bolster

❮ Previous
Next ❯

Citations

Aug 4, 2010·Current Diabetes Reports·Merja Roivainen, Karin Klingel
Sep 7, 2013·Nature Communications·Yiming ZhouMakoto Tominaga
Jun 28, 2011·Proceedings of the National Academy of Sciences of the United States of America·Lukas Adrian BerchtoldJoachim Størling
Oct 29, 2010·The Journal of Biological Chemistry·Fabrice MooreDecio L Eizirik
Oct 14, 2010·Database : the Journal of Biological Databases and Curation·Robin LiechtiIoannis Xenarios
Nov 3, 2011·PLoS Computational Biology·Marko Sysi-AhoMatej Orešič
Jan 29, 2011·Molecular Medicine·Dan P ChristensenThomas Mandrup-Poulsen
Mar 19, 2014·Marine Drugs·Yunlong LiuJianhong Shu
May 3, 2014·Cell Death and Differentiation·D A CunhaM Cnop
Jun 2, 2012·Journal of Transplantation·Valia Bravo-EganaRicardo L Pastori
Sep 18, 2014·Journal of Molecular Endocrinology·Petter VikmanNikolay Oskolkov
Jun 19, 2013·Current Opinion in Endocrinology, Diabetes, and Obesity·Menno van LummelBart O Roep
Jul 2, 2011·Trends in Endocrinology and Metabolism : TEM·Yan Hang, Roland Stein
Dec 3, 2015·European Journal of Endocrinology·Jonàs Juan-MateuDécio L Eizirik
Nov 19, 2013·Immunologic Research·Antonello PileggiRicardo L Pastori
Sep 18, 2013·Diabetes, Obesity & Metabolism·I Santin, D L Eizirik
Feb 3, 2015·Proteomics. Clinical Applications·Inne CrèvecoeurLut Overbergh
Sep 5, 2015·BioMed Research International·Giuliana VentrigliaFrancesco Dotta
Jul 1, 2015·The Journal of Experimental Medicine·Elisabeth K MalleShane T Grey
Jul 31, 2013·Molecular and Cellular Endocrinology·Letícia F TerraMari C Sogayar
Aug 14, 2012·Molecular and Cellular Endocrinology·Mohammed BensellamJean-Christophe Jonas
Apr 2, 2015·Molecular Metabolism·Dhaval PatelBernard Thorens
Nov 21, 2014·Journal of Proteome Research·Dhana G GorasiaAnthony W Purcell

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR

Software Mentioned

IPA
Ingenuity Pathway Analysis ( IPA )
GCRMA
ArrayAssist Exon
Stratagene

Related Concepts

Related Feeds

Alternative splicing

Alternative splicing a regulated gene expression process that allows a single genetic sequence to code for multiple proteins. Here is that latest research.

American Diabetes Association Journals

Discover the latest diabetes research published by the journals from the American Diabetes Association.