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. © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.5867984989Eizirik, D.L., Colli, M.L., Ortis, F., The role of inflammation in insulitis and beta-cell loss in type 1 diabetes (2009) Nat. Rev. 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