ArticleThe Journal of biological chemistry2011
Calcineurin/nuclear factor of activated T cells and MAPK signaling induce TNF-{alpha} gene expression in pancreatic islet endocrine cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Mechanisms inducing differentiation of adult islet progenitor-like cells into functional islet-like organoids.Frontiers in transplantation · 2026Article
- Investigation into the Potential Mechanism of Radix Paeoniae Rubra Against Ischemic Stroke Based on Network Pharmacology.Nutrients · 2024Article
- Calcineurin/NFATc2 and PI3K/AKT signaling maintains β-cell identity and function during metabolic and inflammatory stress.iScience · 2022Article
- MicroRNA-mediated calcineurin signaling activation induces CCL2, CCL3, CCL5, IL8, and chemotactic activities in 4,4'-methylene diphenyl diisocyanate exposed macrophages.Xenobiotica; the fate of foreign compounds in biological systems · 2021Article
- Review
- Loss of MafA and MafB expression promotes islet inflammation.Scientific reports · 2019Article
- Cryptotanshinone Attenuates Oxygen-Glucose Deprivation/ Recovery-Induced Injury in anFrontiers in neurology · 2019Article
- Cellular signaling pathways regulating β-cell proliferation as a promising therapeutic target in the treatment of diabetes.Experimental and therapeutic medicine · 2018Review
- A Common Type 2 Diabetes Risk Variant Potentiates Activity of an Evolutionarily Conserved Islet Stretch Enhancer and Increases C2CD4A and C2CD4B Expression.American journal of human genetics · 2018Article
- Transcriptional regulation of metabolism in disease: From transcription factors to epigenetics.PeerJ · 2018Article
- Pancreatic β-Cell-Derived IP-10/CXCL10 Isletokine Mediates Early Loss of Graft Function in Islet Cell Transplantation.Diabetes · 2017Article
- Anti-high mobility group box-1 (HMGB1) antibody attenuates kidney damage following experimental crush injury and the possible role of the tumor necrosis factor-α and c-Jun N-terminal kinase pathway.Journal of orthopaedic surgery and research · 2017Article
- EPO-cyclosporine combination therapy reduced brain infarct area in rat after acute ischemic stroke: role of innate immune-inflammatory response, micro-RNAs and MAPK family signaling pathway.American journal of translational research · 2017Article
- The Transcription Factor Nfatc2 Regulates β-Cell Proliferation and Genes Associated with Type 2 Diabetes in Mouse and Human Islets.PLoS genetics · 2016Article
- Article
- Effect of lysophosphatidic acid on the immune inflammatory response and the connexin 43 protein in myocardial infarction.Experimental and therapeutic medicine · 2016Article
- Widespread JNK-dependent alternative splicing induces a positive feedback loop through CELF2-mediated regulation of MKK7 during T-cell activation.Genes & development · 2015Article
- Etanercept alleviates early brain injury following experimental subarachnoid hemorrhage and the possible role of tumor necrosis factor-α and c-Jun N-terminal kinase pathway.Neurochemical research · 2015Article
- NFAT targets signaling molecules to gene promoters in pancreatic β-cells.Molecular endocrinology (Baltimore, Md.) · 2015Article
- RNA-Seq reveals a role for NFAT-signaling in human retinal microvascular endothelial cells treated with TNFα.PloS one · 2015Article
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5 authors at 3 institutions in 1 country.
Funding
Abstract
Cytokines contribute to pancreatic islet inflammation, leading to impaired glucose homeostasis and diabetic diseases. A plethora of data shows that proinflammatory cytokines are produced in pancreatic islets by infiltrating mononuclear immune cells. Here, we show that pancreatic islet α cells and β cells express tumor necrosis factor-α (TNF-α) and other cytokines capable of promoting islet inflammation when exposed to interleukin-1β (IL-1β). Cytokine expression by β cells was dependent on calcineurin (CN)/nuclear factor of activated T cells (NFAT) and MAPK signaling. NFAT associated with the TNF-α promoter in response to stimuli and synergistically activated promoter activity with ATF2 and c-Jun. In contrast, the β-cell-specific transcriptional activator MafA could repress NFAT-mediated TNF-α gene expression whenever C/EBP-β was bound to the promoter. NFAT differentially regulated the TNF-α gene depending upon the expression and MAPK-dependent activation of interacting basic leucine zipper partners in β cells. Both p38 and JNK were required for induction of TNF-α mRNA and protein expression. Collectively, the data show that glucose and IL-1β can activate signaling pathways, which control induction and repression of cytokines in pancreatic endocrine cells. Thus, by these mechanisms, pancreatic β cells themselves may contribute to islet inflammation and their own immunological destruction in the pathogenesis of diabetes.
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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.