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- Title
The lysine deacetylase inhibitor Givinostat inhibits β-cell IL-1β induced IL-1β transcription and processing.
- Authors
Dahllöf, Mattias S; Christensen, Dan P; Lundh, Morten; Dinarello, Charles A; Mascagni, Paolo; Grunnet, Lars G; Mandrup-Poulsen, Thomas
- Abstract
Pro-inflammatory cytokines and chemokines, in particular IL-1β, IFNγ, and CXCL10, contribute to β-cell failure and loss in DM via IL-1R, IFNγR, and TLR4 signaling. IL-1 signaling deficiency reduces diabetes incidence, islet IL-1β secretion, and hyperglycemia in animal models of diabetes. Further, IL-1R antagonism improves normoglycemia and β-cell function in type 2 diabetic patients. Inhibition of lysine deacetylases (KDACi) counteracts β-cell toxicity induced by the combination of IL-1 and IFNγ and reduces diabetes incidence in non-obese diabetic (NOD) mice. We hypothesized that KDACi breaks an autoinflammatory circuit by differentially preventing β-cell expression of the β-cell toxic inflammatory molecules IL-1β and CXCL10 induced by single cytokines.
- Publication
Islets, 2012, Vol 4, Issue 6, p417
- ISSN
1938-2022
- Publication type
Journal Article
- DOI
10.4161/isl.23541