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Differential usage of NF‐κB activating signals by IL‐1β and TNF‐α in pancreatic beta cells
Author(s) -
Ortis F.,
Miani M.,
Colli M.L.,
Cunha D.A.,
Gurzov E.N.,
Allagnat F.,
Chariot A.,
Eizirik D.L.
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.02.021
Subject(s) - iκb kinase , tumor necrosis factor alpha , nf κb , nfkb1 , chemistry , microbiology and biotechnology , proteasome , cancer research , signal transduction , biology , endocrinology , biochemistry , gene , transcription factor
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.