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Differential usage of NF-κB activating signals by IL-1β and TNF-α in pancreatic beta cells.
- Source :
-
FEBS letters [FEBS Lett] 2012 Apr 05; Vol. 586 (7), pp. 984-9. Date of Electronic Publication: 2012 Feb 22. - Publication Year :
- 2012
-
Abstract
- The cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α induce β-cell death in type 1 diabetes via NF-κB activation. IL-1β induces a more marked NF-κB activation than TNF-α, with higher expression of genes involved in β-cell dysfunction and death. We show here a differential usage of the IKK complex by IL-1β and TNF-α in β-cells. While TNF-α uses IKK complexes containing both IKKα and IKKβ, IL-1β induces complexes with IKKα only; this effect is achieved by induction of IKKβ degradation via the proteasome. Both IKKγ and activation of the TRAF6-TAK1-JNK pathway are involved in IL-1β-induced IKKβ degradation.<br /> (Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Cell Line
Cells, Cultured
Diabetes Mellitus, Type 1 drug therapy
Gene Silencing
Humans
I-kappa B Kinase antagonists & inhibitors
I-kappa B Kinase genetics
Insulin-Secreting Cells cytology
Insulin-Secreting Cells drug effects
Mice
Molecular Targeted Therapy
Protease Inhibitors pharmacology
Proteasome Inhibitors
Protein Kinase Inhibitors pharmacology
Protein Subunits antagonists & inhibitors
Protein Subunits genetics
Protein Subunits metabolism
Proteolysis drug effects
Rats
Rats, Wistar
Recombinant Proteins metabolism
Tumor Necrosis Factor-alpha genetics
I-kappa B Kinase metabolism
Insulin-Secreting Cells metabolism
Interleukin-1beta metabolism
NF-kappa B metabolism
Proteasome Endopeptidase Complex metabolism
Signal Transduction drug effects
Tumor Necrosis Factor-alpha metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3468
- Volume :
- 586
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- FEBS letters
- Publication Type :
- Academic Journal
- Accession number :
- 22569251
- Full Text :
- https://doi.org/10.1016/j.febslet.2012.02.021