Differential usage of NF-κB activating signals by IL-1β and TNF-α in pancreatic beta cells

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.

► Differential usage of IKK complex components by IL-1β and TNF-α in beta cells.
► The IKK complex induced by IL-1β in beta cells lacks the IKKβ subunit.
► IL-1β, but not TNF-α, induces degradation of IKKβ in pancreatic beta cells.
► IL-1β-induced IKKβ degradation is dependent on proteasome activity and IKKγ.
► IL-1β-induced IKKβ degradation depends on TRAF6-TAK1-JNK activation.