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.

• Authors: Qi Sun, Ruo-Lan Xiang, Yan-Li Yang, Kai Feng, Kui Zhang, Wen-Yi Ding
• Journal: Chinese medical journal (Chin Med J (Engl)) Vol. 126 Issue 21 Pg. 4048-53 (Nov 2013) ISSN: 2542-5641 [Electronic] China
• PMID: 24229672 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Interleukin-1
• STAT1 Transcription Factor
• Socs1 protein, rat
• Suppressor of Cytokine Signaling 1 Protein
• Suppressor of Cytokine Signaling Proteins
• Tumor Necrosis Factor-alpha
• Interferon-gamma
• Janus Kinase 2

Topics

• Animals
• Apoptosis (drug effects, genetics)
• Blotting, Western
• Cell Line
• Cytokines (pharmacology)
• Interferon-gamma (pharmacology)
• Interleukin-1 (pharmacology)
• Islets of Langerhans (cytology, drug effects)
• Janus Kinase 2 (metabolism)
• Phosphorylation (drug effects)
• Rats
• Reverse Transcriptase Polymerase Chain Reaction
• STAT1 Transcription Factor (genetics, metabolism)
• Signal Transduction (drug effects)
• Suppressor of Cytokine Signaling 1 Protein
• Suppressor of Cytokine Signaling Proteins (genetics, metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)