Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta-mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated proapoptotic pathways

Allan Ertman Karlsen, P E Heding, H Frobøse, S G Rønn, M Kruhøffer, T F Orntoft, M Darville, D L Eizirik, F Pociot, J Nerup, Thomas Mandrup-Poulsen, N Billestrup

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Abstract

The proinflammatory cytokine IL-1beta induces apoptosis in pancreatic beta cells via pathways dependent on nuclear factor-kappaB (NF-kappaB), mitogen-activated protein kinase, and protein kinase C. We recently showed suppressor of cytokine signalling (SOCS)-3 to be a natural negative feedback regulator of IL-1beta- and IFN-gamma-mediated signalling in rat islets and beta cell lines, preventing their deleterious effects. However, the mechanisms underlying SOCS-3 inhibition of IL-1beta signalling and prevention against apoptosis remain unknown.
OriginalsprogEngelsk
TidsskriftDiabetologia
Vol/bind47
Udgave nummer11
Sider (fra-til)1998-2011
Antal sider14
ISSN0012-186X
DOI
StatusUdgivet - 1 nov. 2004

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