ArticleJournal of cellular and molecular medicine2016
LIGHT/IFN-γ triggers β cells apoptosis via NF-κB/Bcl2-dependent mitochondrial pathway.
Article in Journal of cellular and molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- The role of vitamin D signalling in β cell apoptosis: a systematic review.Apoptosis : an international journal on programmed cell death · 2026Pooled it
- TNFSF14-HVEM/LTβR Exacerbates Keratinocyte Abnormalities and IMQ-Induced Psoriatic Skin Inflammation via Activating NF-κB/TWIST1 Signalling Pathway.Journal of cellular and molecular medicine · 2025Article
- Advance in molecular mechanisms underlying diabetes related to viral hepatitis infection.Frontiers in cellular and infection microbiology · 2025Review
- Characterization of 3,3'-iminodipropionitrile (IDPN) damaged utricle transcriptome in the adult mouse utricle.Frontiers in molecular neuroscience · 2024Article
- Tumor Necrosis Factor Superfamily 14 (LIGHT) Restricts Neovascularization by Decreasing Circulating Endothelial Progenitor Cells and Function.International journal of molecular sciences · 2023Article
- LIGHT deficiency attenuates acute kidney disease development in an in vivo experimental renal ischemia and reperfusion injury model.Cell death discovery · 2022Article
- Novel therapeutic strategies and perspectives for pancreatic cancer: Autophagy and apoptosis are key mechanisms to fight pancreatic cancer.Medical oncology (Northwood, London, England) · 2021Review
- Good Cop, Bad Cop: The Opposing Effects of Macrophage Activation State on Maintaining or Damaging Functional β-Cell Mass.Metabolites · 2020Review
- LIGHT aggravates sepsis-associated acute kidney injury via TLR4-MyD88-NF-κB pathway.Journal of cellular and molecular medicine · 2020Article
- Endoplasmic reticulum stress and destruction of pancreatic β cells in type 1 diabetes.Chinese medical journal · 2020Review
- TNFSF14: LIGHTing the Way for Effective Cancer Immunotherapy.Frontiers in immunology · 2020Review
- Gamma-tocopherol ameliorates hyperglycemia-induced hepatic inflammation associated with NLRP3 inflammasome in alloxan-induced diabetic mice.Nutrition research and practice · 2019Article
- Transcriptome Sequencing Reveals the Differentially Expressed lncRNAs and mRNAs Involved in Cryoinjuries in Frozen-Thawed Giant Panda (International journal of molecular sciences · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
LIGHT recruits and activates naive T cells in the islets at the onset of diabetes. IFN-γ secreted by activated T lymphocytes is involved in beta cell apoptosis. However, whether LIGHT sensitizes IFNγ-induced beta cells destruction remains unclear. In this study, we used the murine beta cell line MIN6 and primary islet cells as models for investigating the underlying cellular mechanisms involved in LIGHT/IFNγ - induced pancreatic beta cell destruction. LIGHT and IFN-γ synergistically reduced MIN6 and primary islet cells viability; decreased cell viability was due to apoptosis, as demonstrated by a significant increase in Annexin V(+) cell percentage, detected by flow cytometry. In addition to marked increases in cytochrome c release and NF-κB activation, the combination of LIGHT and IFN-γ caused an obvious decrease in expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, but an increase in expression of the pro-apoptotic proteins Bak and Bax in MIN6 cells. Accordingly, LIGHT deficiency led to a decrease in NF-κB activation and Bak expression, and peri-insulitis in non-obese diabetes mice. Inhibition of NF-κB activation with the specific NF-κB inhibitor, PDTC (pyrrolidine dithiocarbamate), reversed Bcl-xL down-regulation and Bax up-regulation, and led to a significant increase in LIGHT- and IFN-γ-treated cell viability. Moreover, cleaved caspase-9, -3, and PARP (poly (ADP-ribose) polymerase) were observed after LIGHT and IFN-γ treatment. Pretreatment with caspase inhibitors remarkably attenuated LIGHT- and IFNγ-induced cell apoptosis. Taken together, our results indicate that LIGHT signalling pathway combined with IFN-γ induces beta cells apoptosis via an NF-κB/Bcl2-dependent mitochondrial pathway.
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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.