ArticleDiabetologia2004
Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1beta-mediated toxicity through inhibition of multiple nuclear factor-kappaB-regulated proapoptotic pathways.
Article in Diabetologia, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 54 citations in OpenAlex.
- Mechanism of herpesvirus protein kinase UL13 in immune escape and viral replication.Frontiers in immunology · 2022Review
- Suppressor of Cytokine Signaling (SOCS)1 Regulates Interleukin-4 (IL-4)-activated Insulin Receptor Substrate (IRS)-2 Tyrosine Phosphorylation in Monocytes and Macrophages via the Proteasome.The Journal of biological chemistry · 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
- Pulmonary inflammation is regulated by the levels of the vesicular acetylcholine transporter.PloS one · 2015Article
- Suppressors of cytokine signaling (SOCS) and type 2 diabetes.Molecular biology reports · 2014Review
- The efficacy of SPA0355 in protecting β cells in isolated pancreatic islets and in a murine experimental model of type 1 diabetes.Experimental & molecular medicine · 2013Article
- Ciliary neurotrophic factor protects mice against streptozotocin-induced type 1 diabetes through SOCS3: the role of STAT1/STAT3 ratio in β-cell death.The Journal of biological chemistry · 2012Article
- Prunella vulgaris aqueous extract attenuates IL-1β-induced apoptosis and NF-κB activation in INS-1 cells.Experimental and therapeutic medicine · 2012Article
- The transcription factor C/EBP delta has anti-apoptotic and anti-inflammatory roles in pancreatic beta cells.PloS one · 2012Article
- Impaired miR-146a expression links subclinical inflammation and insulin resistance in Type 2 diabetes.Molecular and cellular biochemistry · 2011Article
- Effects of Imatinib Mesylate (Gleevec) on human islet NF-kappaB activation and chemokine production in vitro.PloS one · 2011Article
- Suppressor of cytokine signaling (SOCS)-1 is expressed in human prostate cancer and exerts growth-inhibitory function through down-regulation of cyclins and cyclin-dependent kinases.The American journal of pathology · 2009Article
- IL-1beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells.Diabetologia · 2009Article
- Suppressor of cytokine signalling-3 expression inhibits cytokine-mediated destruction of primary mouse and rat pancreatic islets and delays allograft rejection.Diabetologia · 2008Article
- Article
- Neuronal nicotinic alpha7 receptors modulate inflammatory cytokine production in the skin following ultraviolet radiation.Journal of neuroimmunology · 2008Article
- Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe proinflammatory cytokine IL-1beta induces apoptosis in pancreatic beta cells via pathways dependent on nuclear factor-kappaB (NF-kappaB), mitogen-activated protein kinase, and protein kinase C. We recently showed suppressor of cytokine signalling (SOCS)-3 to be a natural negative feedback regulator of IL-1beta- and IFN-gamma-mediated signalling in rat islets and beta cell lines, preventing their deleterious effects. However, the mechanisms underlying SOCS-3 inhibition of IL-1beta signalling and prevention against apoptosis remain unknown.
methodsThe effect of SOCS-3 expression on the global gene-expression profile following IL-1beta exposure was microarray-analysed using a rat beta cell line (INS-1) with inducible SOCS-3 expression. Subsequently, functional analyses were performed.
resultsEighty-two known genes and several expressed sequence tags (ESTs) changed expression level 2.5-fold or more in response to IL-1beta alone. Following 6 h of IL-1beta exposure, 23 transcripts were up-regulated. Of these, several, including all eight transcripts relating to immune/inflammatory response pathways, were suppressed by SOCS-3. Following 24 h of IL-1beta exposure, secondary response genes were detected, affecting metabolism, energy generation, protein synthesis and degradation, growth arrest, and apoptosis. The majority of these changes were prevented by SOCS-3 expression. Multiple IL-1beta-induced NF-kappaB-dependent proapoptotic early response genes were inhibited by SOCS-3 expression, suggesting that SOCS-3 inhibits NF-kappaB-mediated signalling. These observations were experimentally confirmed in functional analyses. CONCLUSIONS/
interpretationThis study suggests that there is an unexpected cross-talk between the SOCS/IFN and the IL-1beta pathways of signalling in pancreatic beta cells, which could lead to a novel perspective of blocking two important proapoptotic pathways in pancreatic beta cells by influencing a single signalling molecule, namely SOCS-3.
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