Protective Role of Complement C3 Against Cytokine-Mediated β-Cell Apoptosis.

ABSTRACT: Type 1 diabetes is a chronic autoimmune disease characterized by pancreatic islet inflammation and β-cell destruction by proinflammatory cytokines and other mediators. Based on RNA sequencing and protein-protein interaction analyses of human islets exposed to proinflammatory cytokines, we identified complement C3 as a hub for some of the effects of cytokines. The proinflammatory cytokines interleukin-1β plus interferon-γ increase C3 expression in rodent and human pancreatic β-cells, and C3 is detected by histology in and around the islets of diabetic patients. Surprisingly, C3 silencing exacerbates apoptosis under both basal condition and following exposure to cytokines, and it increases chemokine expression upon cytokine treatment. C3 exerts its prosurvival effects via AKT activation and

SUBMITTER: Dos Santos RS 

PROVIDER: S-EPMC5551554 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature