Suppressor of cytokine signaling 1 protects rat pancreatic islets from cytokine-induced apoptosis through Janus kinase/signal transducers and activators of transcription pathway

Abstract

Background: Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathway involved in negative feedback loops. Although SOCS1 is an important intracellular suppressor of apoptosis in a variety of cell types, its role in cytokine-induced pancreatic β-cell apoptosis remains unclear. The present study investigated potential effects of SOCS1 on the cytokine-induced pancreatic β-cell apoptosis.

Methods: After successfully transfected with SOCS1/pEGFP-C1 or pEGFP-C1 plasmids to overexpress SOCS1, RINm5F (rat insulinoma cell line) cells were exposed to cytokines, interferon (IFN)-γ alone, IFN-γ+interleukin (IL)-1β, IFN-β+IL-1β+tumor necrosis factor (TNF)-α respectively. Pancreatic β-cell apoptosis was assessed by using MTT, FACS, and caspase-3 activity assays. Protein phosphorylation of Janus kinase 2 (JAK2) and signal transducers and activators of transcription 1 (STAT1) were verified by Western blotting and mRNA expression of inducible nitric oxide synthase (iNOS), NF-κB and Fas were analyzed by RT-PCR.

Results: Overexpression of SOCS1 in RINm5F cells was shown to attenuate IFN-γ alone, IFN-γ+IL-1β and IFN-γ+TNF-α+IL-1β mediated apoptosis. Phosphorylation of JAK2 and STAT1 significantly decreased in RINm5F cells which overexpressed SOCS1 protein. Overexpression of SOCS1 significantly suppressed cytokine-induced iNOS mRNA levels.

Conclusion: Overexpression of SOCS1 protects pancreatic islets from cytokine-induced cell apoptosis via the JAK2/STAT1 pathway.