Differential usage of NF-kappa B activating signals by IL-1 beta and TNF-alpha in pancreatic beta cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)The cytokines interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha induce beta-cell death in type 1 diabetes via NF-kappa B activation. IL-1 beta induces a more marked NF-kappa B activation than TNF-alpha, with higher expression of genes involved in beta-cell dysfunction and death. We show here a differential usage of the IKK complex by IL-1 beta and TNF-alpha in beta-cells. While TNF-alpha uses IKK complexes containing both IKK alpha and IKK beta, IL-1 beta induces complexes with IKKa only; this effect is achieved by induction of IKK beta degradation via the proteasome. Both IKK gamma and activation of the TRAF6-TAK1-JNK pathway are involved in IL-1 beta-induced IKK beta degradation. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.5867984989Fonds National de la Recherche Scientifique (FNRS) BelgiumCommunaute Francaise de Belgique - Actions de Recherche Concertees (ARC)European UnionDutch Diabetes Research Foundation [2008.40.001]Belgium Program on Interuniversity Poles of Attraction [IUAP P6/40]Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES