ArticleThe Journal of endocrinology2017
The immunoproteasome is induced by cytokines and regulates apoptosis in human islets.
Article in The Journal of endocrinology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 34 citations in OpenAlex.
- The role of immunoproteasome in diabetes and diabetes-related complications.Genes & diseases · 2026Review
- Multi-omic human pancreatic islet endoplasmic reticulum and cytokine stress response mapping provides type 2 diabetes genetic insights.Cell metabolism · 2024Article
- IFNɣ but not IFNα increases recognition of insulin defective ribosomal product-derived antigen to amplify islet autoimmunity.Diabetologia · 2023Article
- Type 1 diabetes risk genes mediate pancreatic beta cell survival in response to proinflammatory cytokines.Cell genomics · 2022Article
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- Making Insulin and Staying Out of Autoimmune Trouble: The Beta-Cell Conundrum.Frontiers in immunology · 2021Review
- Proinflammatory Cytokines Perturb Mouse and Human Pancreatic Islet Circadian Rhythmicity and Induce Uncoordinated β-Cell Clock Gene Expression via Nitric Oxide, Lysine Deacetylases, and Immunoproteasomal Activity.International journal of molecular sciences · 2020Article
- The Effects of Immune System Modulation on Prion Disease Susceptibility and Pathogenesis.International journal of molecular sciences · 2020Review
- Accelerated onset of CNS prion disease in mice co-infected with a gastrointestinal helminth pathogen during the preclinical phase.Scientific reports · 2020Article
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- Regulation of Proteasome Activity by (Post-)transcriptional Mechanisms.Frontiers in molecular biosciences · 2019Review
- Islet stress, degradation and autoimmunity.Diabetes, obesity & metabolism · 2018Review
- Immunoproteasomes as a novel antiviral mechanism in rhinovirus-infected airways.Clinical science (London, England : 1979) · 2018Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
In addition to degrading misfolded and damaged proteins, the proteasome regulates the fate of cells in response to stress. The role of the proteasome in pro-inflammatory cytokine-induced human beta-cell apoptosis is unknown. Using INS-1, INS-1E and human islets exposed to combinations of IFNγ, IL-1β and TNFα with or without addition of small molecules, we assessed the role of the immunoproteasome in pancreatic beta-cell demise. Here, we show that cytokines induce the expression and activity of the immuno-proteasome in INS-1E cells and human islets. Cytokine-induced expression of immuno-proteasome subunits, but not activity, depended upon histone deacetylase 3 activation. Inhibition of JAK1/STAT1 signaling did not affect proteasomal activity. Inhibition of the immuno-proteasome subunit PSMB8 aggravated cytokine-induced human beta-cell apoptosis while reducing intracellular levels of oxidized proteins in INS-1 cells. While cytokines increased total cellular NFκB subunit P50 and P52 levels and reduced the cytosolic NFκB subunit P65 and IκB levels, these effects were unaffected by PSMB8 inhibition. We conclude that beta cells upregulate immuno-proteasome expression and activity in response to IFNγ, likely as a protective response to confine inflammatory signaling.
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Registered trials
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.