Variations in IB1/JIP1 expression regulate susceptibility of beta-cells to cytokine-induced apoptosis irrespective of C-Jun NH2-terminal kinase signaling.

Details

Serval ID
serval:BIB_78FD74B434BB
Type
Article: article from journal or magazin.
Collection
Publications
Title
Variations in IB1/JIP1 expression regulate susceptibility of beta-cells to cytokine-induced apoptosis irrespective of C-Jun NH2-terminal kinase signaling.
Journal
Diabetes
Author(s)
Ling Z., Van de Casteele M., Dong J., Heimberg H., Haefliger J.A., Waeber G., Schuit F., Pipeleers D.
ISSN
0012-1797
Publication state
Published
Issued date
2003
Peer-reviewed
Oui
Volume
52
Number
10
Pages
2497-502
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
We previously reported that interleukin-1beta (IL-1beta) alone does not cause apoptosis of beta-cells, whereas when combined with gamma-interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), it exerts a distinct apoptotic effect. Studies in beta-cell lines indicated that IL-1beta reduced expression of islet brain (IB)-1/JNK interacting protein (JIP)-1, a JNK scaffold protein with antiapoptotic action. We examined whether variations in IB1/JIP-1 expression in purified primary beta-cells affect their susceptibility to cytokine-induced apoptosis. Exposure to IL-1beta for 24 h decreased cellular IB1/JIP-1 content by 66 +/- 17%; this IL-1beta effect was maintained in the presence of TNF-alpha + IFN-gamma, which did not influence IB1/JIP-1 levels by themselves. Addition of IL-1beta to TNF-alpha + IFN-gamma increased apoptosis from 20 +/- 2% to 59 +/- 5%. A similar increase in TNF-alpha + IFN-gamma-induced apoptosis was produced by adenoviral expression of antisense IB1/JIP-1 and was not further enhanced by addition of IL-1beta, indicating that IL-1beta-mediated suppression of IB1/JIP-1 in beta-cells increases their susceptibility to cytokine-induced apoptosis. However, adenovirally mediated overexpression of IB1/JIP-1 also potentiated TNF-alpha + IFN-gamma-induced apoptosis, suggesting that the antiapoptotic effect of IB1/JIP-1 depends on well-defined cellular levels. We conclude that the IB1/JIP-1 level in beta-cells can control their susceptibility to apoptosis independent of JNK signaling.
Keywords
Adaptor Proteins, Signal Transducing, Animals, Apoptosis, Carrier Proteins, Cells, Cultured, Cytokines, Drug Administration Schedule, Drug Combinations, Drug Synergism, Gene Transfer Techniques, Humans, Interferon-gamma, Interleukin-1, Islets of Langerhans, JNK Mitogen-Activated Protein Kinases, Male, Mitogen-Activated Protein Kinases, Nuclear Proteins, Rats, Rats, Wistar, Recombinant Proteins, Signal Transduction, Trans-Activators, Tumor Necrosis Factor-alpha
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 13:48
Last modification date
20/08/2019 14:35
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