Document Detail


TNFalpha and IFNgamma potentiate IL-1beta induced mitogen activated protein kinase activity in rat pancreatic islets of Langerhans.
MedLine Citation:
PMID:  11126408     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
N A Andersen; C M Larsen; T Mandrup-Poulsen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Diabetologia     Volume:  43     ISSN:  0012-186X     ISO Abbreviation:  Diabetologia     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-12-20     Completed Date:  2001-02-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1389-96     Citation Subset:  IM    
Affiliation:
Steno Diabetes Center, Gentofte, Denmark.
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MeSH Terms
Descriptor/Qualifier:
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:
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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