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


CONCLUSIONS
Overexpression of SOCS1 protects pancreatic islets from cytokine-induced cell apoptosis via the JAK2/STAT1 pathway.
Department of Endocrinology, Key Laboratory of Endocrinology Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China. Email: qisun50@hotmail.com.
Qi
Q
Sun
Ruo-Lan
RL
Xiang
Yan-Li
YL
Yang
Kai
K
Feng
Kui
K
Zhang
Wen-Yi
WY
Ding
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects; D053614:Janus Kinase 2 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D050794:STAT1 Transcription Factor; C491589:Socs1 protein, rat; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D053614:Janus Kinase 2