Differential usage of NF-kB activating signals by IL-1b and TNF-a in pancreatic beta cells

The cytokines interleukin (IL)-1b and tumor necrosis factor (TNF)-a induce b-cell death in type 1 diabetes via NF-kB activation. IL-1b induces a more marked NF-kB activation than TNF-a, with higher expression of genes involved in b-cell dysfunction and death. We show here a differential usage of the IKK complex by IL-1b and TNF-a in b-cells. While TNF-a uses IKK complexes containing both IKKa and IKKb, IL-1b induces complexes with IKKa only; this effect is achieved by induction of IKKb degradation via the proteasome. Both IKKg and activation of the TRAF6-TAK1-JNK pathway are involved in IL-1b-induced IKKb degradation.