Intracellular C3 protects β-cells from IL-1β-driven cytotoxicity via interaction with Fyn-related kinase.

ABSTRACT: One of the hallmarks of type 1 but also type 2 diabetes is pancreatic islet inflammation, associated with altered pancreatic islet function and structure, if unresolved. IL-1β is a proinflammatory cytokine which detrimentally affects β-cell function. In the course of diabetes, complement components, including the central complement protein C3, are deregulated. Previously, we reported high C3 expression in human pancreatic islets, with upregulation after IL-1β treatment. In the current investigation, using primary human and rodent material and CRISPR/Cas9 gene-edited β-cells deficient in C3, or producing only cytosolic C3 from a noncanonical in-frame start codon, we report a protective effect of C3 against IL-1β-induced β-cell death, that is attributed to the cytosolic fraction of C3. Furth

SUBMITTER: Kulak K 

PROVIDER: S-EPMC10895342 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature