ArticleProceedings of the National Academy of Sciences of the United States of America2001
Suppressor of cytokine signaling 3 (SOCS-3) protects beta -cells against interleukin-1beta - and interferon-gamma -mediated toxicity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.
- Higher Dietary Inflammatory Index Scores Increase the Risk of Diabetes Mellitus: A Meta-Analysis and Systematic Review.Frontiers in endocrinology · 2021Pooled it
- A surviving beta cell subpopulation enriched in patients with T1D.bioRxiv : the preprint server for biology · 2026Article
- An Update Comprehensive Review on Epigenetic Modifications and Therapies in Autoimmune Diseases.Clinical reviews in allergy & immunology · 2026Review
- New insight into the role of SOCS family in immune regulation and autoimmune pathogenesis.Journal of advanced research · 2026Review
- Inhibition of pyrimidine de novo synthesis fosters Treg cells and reduces diabetes development in models of Type 1 Diabetes.Molecular metabolism · 2025Article
- Diet-induced inflammation is associated with fatty pancreas in patients with common bile duct stones.Scientific reports · 2025Article
- Corneal application of SOCS1/3 peptides for the treatment of eye diseases mediated by inflammation and oxidative stress.Frontiers in immunology · 2024Review
- Role of SOCS and VHL Proteins in Neuronal Differentiation and Development.International journal of molecular sciences · 2023Review
- Excitotoxic stimulation activates distinct pathogenic and protective expression signatures in the hippocampus.Journal of cellular and molecular medicine · 2021Article
- A novel approach to managing COVID-19 patients; results of lopinavir plus doxycycline cohort.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2021Article
- Article
- MicroRNAs and histone deacetylase inhibition-mediated protection against inflammatory β-cell damage.PloS one · 2018Article
- Effect of Cytokine Signaling 3 Gene Polymorphisms in Childhood Obesity.Journal of clinical research in pediatric endocrinology · 2016Article
- Conditional ablation of HDAC3 in islet beta cells results in glucose intolerance and enhanced susceptibility to STZ-induced diabetes.Oncotarget · 2016Article
- Suppressors of Cytokine Signaling in Sickness and in Health of Pancreatic β-Cells.Frontiers in immunology · 2016Review
- Islet Stellate Cells Isolated from Fibrotic Islet of Goto-Kakizaki Rats Affect Biological Behavior of Beta-Cell.Journal of diabetes research · 2016Article
- Role of ZAC1 in transient neonatal diabetes mellitus and glucose metabolism.World journal of biological chemistry · 2015Review
- Differentially Expressed MicroRNA-483 Confers Distinct Functions in Pancreatic β- and α-Cells.The Journal of biological chemistry · 2015Article
- Though Active on RINm5F Insulinoma Cells and Cultured Pancreatic Islets, Recombinant IL-22 Fails to Modulate Cytotoxicity and Disease in a Protocol of Streptozotocin-Induced Experimental Diabetes.Frontiers in pharmacology · 2015Article
- INS-1 cells inhibit the production of extracellular matrix from pancreatic stellate cells.Journal of molecular histology · 2014Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Suppressor of cytokine signaling 3 (SOCS-3) is a negative feedback regulator of IFN-gamma signaling, shown up-regulated in mouse bone marrow cells by the proinflammatory cytokines interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and IFN-gamma. IL-1beta and IFN-gamma alone, or potentiated by TNF-alpha, are cytotoxic to the insulin producing pancreatic beta-cells and beta-cell lines in vitro and suggested to contribute to the specific beta-cell destruction in Type-1 diabetes mellitus (T1DM). Using a doxycycline-inducible SOCS-3 expression system in the rat beta-cell line INS-1, we demonstrate that the toxic effect of both IL-1beta or IFN-gamma at concentrations that reduced the viability by 50% over 3 days, was fully preventable when SOCS-3 expression was turned on in the cells. At cytokine concentrations or combinations more toxic to the cells, SOCS-3 overexpression yielded a partial protection. Whereas SOCS-3-mediated inhibition of IFN-gamma signaling is described in other cell systems, SOCS-3 mediated inhibition of IL-1beta signaling has not previously been described. In addition we show that SOCS-3 prevention of IL-1beta-induced toxicity is accompanied by inhibited transcription of the inducible nitric oxide synthase (iNOS) by 80%, resulting in 60% decreased formation of the toxic nitric oxide (NO). Analysis of isolated native rat islets exposed to IL-1beta revealed a naturally occurring but delayed up-regulated SOCS-3 transcription. Influencing SOCS-3 expression thus represents an approach for affecting cytokine-induced signal transduction at a proximal step in the signal cascade, potentially useful in future therapies aimed at reducing the destructive potential of beta-cell cytotoxic cytokines in T1DM, as well as other cytokine-dependent diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.