title: Differential usage of NF-κB activating signals by IL-1β and TNF-α in pancreatic beta cells.
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.
authors.affiliation: Laboratory of Experimental Medicine, Université Libre de Bruxelles, Brussels, Belgium. fernandaortis@hotmail.com
authors.forename: F
authors.initials: F
authors.lastname: Ortis
authors.forename: M
authors.initials: M
authors.lastname: Miani
authors.forename: M L
authors.initials: ML
authors.lastname: Colli
authors.forename: D A
authors.initials: DA
authors.lastname: Cunha
authors.forename: E N
authors.initials: EN
authors.lastname: Gurzov
authors.forename: F
authors.initials: F
authors.lastname: Allagnat
authors.forename: A
authors.initials: A
authors.lastname: Chariot
authors.forename: D L
authors.initials: DL
authors.lastname: Eizirik
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D020868:Gene Silencing; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: C508585:IL1B protein, human; D053583:Interleukin-1beta; D016328:NF-kappa B; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D047428:Protein Kinase Inhibitors; D021122:Protein Subunits; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D051550:I-kappa B Kinase; D046988:Proteasome Endopeptidase Complex