ArticlePloS one2015
STAT1-mediated down-regulation of Bcl-2 expression is involved in IFN-γ/TNF-α-induced apoptosis in NIT-1 cells.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Beyond CD30: Dual-Targeting of Malignant and Regulatory T Cells by Brentuximab Vedotin Remodels the Lymphoma Microenvironment and Overcomes Resistance via BCL2 Inhibition in Mycosis Fungoides.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dual role of IFNγ in reprogramming the undifferentiated pleomorphic sarcoma cell line JBT19 towards cytotoxic chemotherapy and antitumor immunity.Oncology letters · 2026Article
- Radiotherapy for overcoming immune checkpoint inhibitor resistance in esophageal squamous cell carcinoma.Frontiers in immunology · 2026Review
- Radiation regulates the expression of HLA-I in esophageal squamous cell carcinoma through interferon-γ.Scientific reports · 2025Article
- Improving the Accumulation and Solubility of Human Interferon-γ (hIFN-γ) in Escherichia coli: A Fusion Protein-Based Method and Network Pharmacology Analysis.Applied biochemistry and biotechnology · 2025Article
- Research and development prospects of TRIM65.Journal of cancer research and clinical oncology · 2025Review
- Emerging role of the cGAS-STING pathway in cardiovascular diseases: biologic function, mechanisms and targeted therapy.Molecular medicine (Cambridge, Mass.) · 2025Review
- Fludarabine attenuates inflammation and dysregulated autophagy in alveolar macrophages via inhibition of STAT1/IRF1 pathway.Laboratory animal research · 2025Article
- Exploring the potential anti-apoptotic effects of traditional Chinese medicine in intervertebral disc degeneration: mechanisms and therapeutic prospects.Frontiers in physiology · 2025Review
- The Counteracting Effects of Ang II and Ang-(1-7) on the Function andGrowth of Insulin-secreting NIT-1 Cells.Current diabetes reviews · 2024Article
- How the Innate Immune DNA Sensing cGAS-STING Pathway Is Involved in Apoptosis.International journal of molecular sciences · 2023Review
- Bolstering the secretion and bioactivities of umbilical cord MSC-derived extracellular vesicles with 3D culture and priming in chemically defined media.Nano convergence · 2022Article
- The multi-kinase inhibitor afatinib serves as a novel candidate for the treatment of human uveal melanoma.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- Good Cop, Bad Cop: The Opposing Effects of Macrophage Activation State on Maintaining or Damaging Functional β-Cell Mass.Metabolites · 2020Review
- IFN‑γ induces apoptosis in human melanocytes by activating the JAK1/STAT1 signaling pathway.Molecular medicine reports · 2020Article
- STAT1-p53-p21axis-dependent stress-induced progression of chronic nephrosis in adriamycin-induced mouse model.Annals of translational medicine · 2020Article
- Article
- Transmembrane and Ubiquitin-Like Domain Containing 1 Protein (TMUB1) Negatively Regulates Hepatocellular Carcinoma Proliferation via Regulating Signal Transducer and Activator of Transcription 1 (STAT1).Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Activation of STAT1 by the FRK tyrosine kinase is associated with human glioma growth.Journal of neuro-oncology · 2019Article
- The ESCRT-Related ATPase Vps4 Is Modulated by Interferon during Herpes Simplex Virus 1 Infection.mBio · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor (TNF)-α and interferon (IFN)-γ are the major pro-inflammatory cytokines involved in beta-cell destruction. The fate of islet beta-cells in the cytokine-induced intrinsic mitochondrial apoptotic pathway is determined by the interaction between members of the Bcl-2 family. However, the mechanism through which beta-cell apoptosis is regulated remains unclear. In this study, we treated the murine beta-cell line NIT-1 with TNF-α and IFN-γ and then investigated the regulation of signal transducer and activator of transcription-1 (STAT-1) and expression of the members of the Bcl-2 family in this apoptotic pathway. Results showed that TNF-α and IFN-γ synergistically reduced NIT-1 cell viability. In addition, the decrease in cell growth was due to apoptosis as shown by apoptotic body formation, detected by confocal laser microscope, and a significant increase in Annexin-Vup(+) cell percentage, detected by flow cytometry. Combination treatment with TNF-α and IFN-γ caused a remarkable increase in the release of cytochrome c, and in the activation of caspase-9 and caspase-3, as well as, an obvious enhancement in STAT-1 phosphorylation; the treatment, however, resulted in the down-regulation in Bcl-2 expression. The enhancement in STAT-1 activity and a down-regulation in Bcl-2 expression was also observed in MIN6 cells, another murine beta-cell derived line, after cells exposure to the combination of TNF-α and IFN-γ treatment. Knockdown of STAT-1 gene expression by siRNA or inhibition of STAT-1 activation with fludarabine reversed Bcl-2 down-expression and led to a significant decrease in apoptosis in TNF-α- and IFN-γ-treated NIT-1 cells. Taken together, our results suggest that STAT1-mediated down-regulation of Bcl-2 is involved in NIT-1 cell apoptosis induced by combination treatment with TNF-α and IFN-γ.
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