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.
Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
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
-
I-kappa B Kinase / metabolism*
-
Insulin-Secreting Cells / cytology
-
Insulin-Secreting Cells / drug effects
-
Insulin-Secreting Cells / metabolism*
-
Interleukin-1beta / metabolism*
-
Mice
-
Molecular Targeted Therapy
-
NF-kappa B / metabolism*
-
Protease Inhibitors / pharmacology
-
Proteasome Endopeptidase Complex / metabolism*
-
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
-
Signal Transduction* / drug effects
-
Tumor Necrosis Factor-alpha / genetics
-
Tumor Necrosis Factor-alpha / metabolism*
Substances
-
IL1B protein, human
-
Interleukin-1beta
-
NF-kappa B
-
Protease Inhibitors
-
Proteasome Inhibitors
-
Protein Kinase Inhibitors
-
Protein Subunits
-
Recombinant Proteins
-
Tumor Necrosis Factor-alpha
-
I-kappa B Kinase
-
Proteasome Endopeptidase Complex