ArticleCell death & disease2018
TNFα sensitizes hepatocytes to FasL-induced apoptosis by NFκB-mediated Fas upregulation.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Effects of Flavonoid Supplementation on Nanomaterial-Induced Toxicity: A Meta-Analysis of Preclinical Animal Studies.Frontiers in nutrition · 2022Pooled it
- Deconstructing the RAGE signaling maze: the molecular key to opening a new dimension of ovarian anti-aging.Experimental & molecular medicine · 2026Review
- Hepatocyte-Derived Apoptotic Bodies as Pathological Intercellular Messengers in the Liver.Biomolecules · 2026Review
- Mechanistic insights into neutrophil involvement in liver transplant ischemia-reperfusion injury and rejection.Frontiers in immunology · 2026Review
- Evaluation of serum levels of CRP and TNF-α in dogs infected withOpen veterinary journal · 2025Article
- Platelet aggregation elicits FasL expression and hepatocyte apoptosis in sinusoidal obstruction syndrome.Scientific reports · 2025Article
- Biomimetic culture substrates for modelling homeostatic intestinal epithelium in vitro.Nature communications · 2025Article
- In vivo and in silico studies on the potential role of garden cress oil in attenuating methotrexate-induced inflammation and apoptosis in liver.Scientific reports · 2025Article
- Decellularized Liver Matrices for Expanding the Donor Pool-An Evaluation of Existing Protocols and Future Trends.Biomolecules · 2025Review
- Predictive Modeling of the Risk of Hyperglycemia in Psoriasis Patients Using Machine Learning: A Multicenter Retrospective Study.Clinical, cosmetic and investigational dermatology · 2025Article
- Mechanisms of retinal photoreceptor loss in spontaneously hypertensive rats.Experimental eye research · 2024Article
- Developing innovative strategies of tumor‑infiltrating lymphocyte therapy for tumor treatment.Oncology reports · 2024Review
- Review
- Targeting adrenergic receptors to mitigate invariant natural killer T cells-induced acute liver injury.iScience · 2023Article
- EMT and Inflammation: Crossroads in HCC.Journal of gastrointestinal cancer · 2023Review
- Microsomal Prostaglandin E Synthase-1 and -2: Emerging Targets in Non-Alcoholic Fatty Liver Disease.International journal of molecular sciences · 2023Review
- Resistance of Human Liver Mesenchymal Stem Cells to FAS-Induced Cell Death.Current issues in molecular biology · 2022Article
- Therapeutic Effect of Crocin on the NASH Model by Targeting the Fas Receptor Signaling Pathway.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2022Article
- Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease.Journal of hepatology · 2022Article
- Ameliorating Effect on Glycolipid Metabolism ofOxidative medicine and cellular longevity · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
Abstract
Although it is well established that TNFα contributes to hepatitis, liver failure and associated hepatocarcinogenesis via the regulation of inflammation, its pro-apoptotic role in the liver has remained enigmatic. On its own, TNFα is unable to trigger apoptosis. However, when combined with the transcriptional inhibitor GaLN, it can cause hepatocyte apoptosis and liver failure in mice. Moreover, along with others, we have shown that TNFα is capable of sensitizing cells to FasL- or drug-induced cell death via c-Jun N-terminal kinase (JNK) activation and phosphorylation/activation of the BH3-only protein Bim. In this context, TNFα could exacerbate hepatocyte cell death during simultaneous inflammatory and T-cell-mediated immune responses in the liver. Here we show that TNFα sensitizes primary hepatocytes, established hepatocyte cell lines and mouse embryo fibroblasts to FasL-induced apoptosis by the transcriptional induction and higher surface expression of Fas via the NFκB pathway. Genetic deletion, diminished expression or dominant-negative inhibition of the NFκB subunit p65 resulted in lower Fas expression and inhibited TNFα-induced Fas upregulation and sensitization to FasL-induced cell death. By hydrodynamic injection of p65 shRNA into the tail vein of mice, we confirm that Fas upregulation by TNFα is also NFκB-mediated in the liver. In conclusion, TNFα sensitization of FasL-induced apoptosis in the liver proceeds via two parallel signaling pathways, activation of JNK and Bim phosphorylation and NFκB-mediated Fas upregulation.
Indexed as
Identifiers
What OpenQuestion holds
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.