| TNFalpha and IFNgamma potentiate IL-1beta induced mitogen activated protein kinase activity in rat pancreatic islets of Langerhans. | |
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MedLine Citation:
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PMID: 11126408 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS/HYPOTHESIS: Interleukin-1 beta (IL-1beta) in synergy with tumour necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma) is cytotoxic to pancreatic beta cells. Mitogen-activated protein kinase (MAPK) activity that is induced by interleukin-1 beta has been suggested to signal nitric oxide-dependent as well as nitric oxide-independent beta-cell destructive pathways. The aim of this study was to investigate if TNFalpha and IFNgamma signal through mitogen-activated protein kinases in isolated rat islets of Langerhans and if they potentiate mitogen-activated protein kinase activity induced by IL-1beta. METHODS: Islets of Langerhans were isolated from 5- to 7-day-old Wistar rats and precultured for 7 days before stimulation with IL-1beta, TNFalpha and/or IFNgamma for 20 min followed by lysis. Kinase activity was measured with a whole cell lysate kinase assay and after immunoprecipitation of the kinase using immunocomplex kinase assay. RESULTS: Exposure to IL-1beta or TNFalpha significantly increased mitogen-activated protein kinase activity, whereas IFNgamma tended to decrease extracellular-signal-regulated kinase activity. Further, TNFalpha and IFNgamma were found to synergistically increase mitogen-activated protein kinase activity induced by IL-1beta. CONCLUSION/INTERPRETATION: We hypothesise that the synergistic effect of IL-1beta, TNFalpha and IFNgamma in the functional inhibition and induction of cell death in pancreatic beta cells is signalled through a synergistic activation of mitogen-activated protein kinase activity. |
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Authors:
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N A Andersen; C M Larsen; T Mandrup-Poulsen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Diabetologia Volume: 43 ISSN: 0012-186X ISO Abbreviation: Diabetologia Publication Date: 2000 Nov |
Date Detail:
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Created Date: 2000-12-20 Completed Date: 2001-02-08 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0006777 Medline TA: Diabetologia Country: Germany |
Other Details:
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Languages: eng Pagination: 1389-96 Citation Subset: IM |
Affiliation:
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Steno Diabetes Center, Gentofte, Denmark. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Activating Transcription Factor 2 Animals Cell Death Culture Techniques Cyclic AMP Response Element-Binding Protein / metabolism DNA-Binding Proteins* Drug Synergism Enzyme Induction HSP27 Heat-Shock Proteins Heat-Shock Proteins* Humans Immunosorbent Techniques Interferon-gamma / pharmacology* Interleukin-1 / pharmacology* Islets of Langerhans / enzymology* Mitogen-Activated Protein Kinases / metabolism* Neoplasm Proteins / metabolism Phosphorylation Proto-Oncogene Proteins / metabolism Rats Rats, Inbred WF Signal Transduction Transcription Factors / metabolism Tumor Necrosis Factor-alpha / pharmacology* ets-Domain Protein Elk-1 |
| Chemical | |
Reg. No./Substance:
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0/Activating Transcription Factor 2; 0/Cyclic AMP Response Element-Binding Protein; 0/DNA-Binding Proteins; 0/Elk1 protein, rat; 0/HSP27 Heat-Shock Proteins; 0/HSPB1 protein, human; 0/Heat-Shock Proteins; 0/Hspb1 protein, rat; 0/Interleukin-1; 0/Neoplasm Proteins; 0/Proto-Oncogene Proteins; 0/Transcription Factors; 0/Tumor Necrosis Factor-alpha; 0/ets-Domain Protein Elk-1; 82115-62-6/Interferon-gamma; EC 2.7.11.24/Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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