ArticleAging cell2022
TNF-α/IFN-γ synergy amplifies senescence-associated inflammation and SARS-CoV-2 receptor expression via hyper-activated JAK/STAT1.
Article in Aging cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 2 of them syntheses that pooled it.
What it found
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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
80 citing papers in PubMed, 2 syntheses or guidelines pooled it, 107 citations in OpenAlex.
- A systematic review of tumor necrosis factor-α blockers, anti-interleukins, and small molecule inhibitors for dissecting cellulitis of the scalp treatment.Orphanet journal of rare diseases · 2025Pooled it
- Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome in patients with COVID-19 infection: is there a link? A systematic review and case report analysis.Journal of neurology · 2023Pooled it
- Cytokine-induced senescence in tumors is based on sustained activation of STAT1- and NFκB-dependent gene regulatory signatures.GeroScience · 2026Article
- TRF2 enriched cytoplasmic chromatin drives cGAS-STAT1-mediated inflammation in senescence.iScience · 2026Article
- Epithelial-immune interface in asthma: Mechanistic insights driving novel therapeutic strategies.Seminars in immunopathology · 2026Review
- BIENs: biomimetic interface encoding on FeMikrochimica acta · 2026Article
- Inflammaging Beyond Biomarkers: Molecular Mechanisms and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- A multifunctional nano-hydrogel attenuates skin photoaging via regulating ECM microenvironment homeostasis.Materials today. Bio · 2026Article
- Pathogen-specific immune responses might underlie divergent outcomes of coronavirus and influenza infection in the natural porcine host.Communications biology · 2026Article
- Viral Mechanisms and Drug Influences on Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) Pathway in Human Coronaviruses Infection: A Systematic Review.Health science reports · 2026Review
- Pathogenic analysis of post-transplantation obesity: A comprehensive systematic review.World journal of transplantation · 2026Article
- Article
- Ultrastructural Features, Immune Response, and Junctional Proteins in the Seminiferous Epithelium of SARS-CoV-2-Infected Mice.International journal of molecular sciences · 2026Article
- Oral microbiome-SASP-aging axis: mechanisms and targeted intervention strategies for age-related diseases.Journal of oral microbiology · 2026Review
- Machine learning integration of bulk and single-cell RNA-Seq data reveals COPS2 as a central immune regulator in deep vein thrombosis.American journal of translational research · 2026Article
- Pathogenesis of Osteoarthritis: Mechanisms of Action of Disulfidptosis and Targeted Therapeutic Strategies.Drug design, development and therapy · 2026Review
- Mechanisms and management of pegylated interferon-α toxicity in chronic hepatitis B.Frontiers in immunology · 2026Review
- SARS-CoV-2 spike S1-mediated HIF-2α activation in retinal endothelial cells suggests a mechanism contributing to post-COVID endothelial dysfunction.Frontiers in immunology · 2026Article
- Novel GS5 sericin mitigates UVA-induced photoaging by activating Nrf2 and inhibiting the JAK-STAT pathway.International journal of biological sciences · 2026Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Older age and underlying conditions such as diabetes/obesity or immunosuppression are leading host risk factors for developing severe complications from COVID-19 infection. The pathogenesis of COVID-19-related cytokine storm, tissue damage, and fibrosis may be interconnected with fundamental aging processes, including dysregulated immune responses and cellular senescence. Here, we examined effects of key cytokines linked to cellular senescence on expression of SARS-CoV-2 viral entry receptors. We found exposure of human umbilical vein endothelial cells (HUVECs) to the inflammatory cytokines, TNF-α + IFN-γ or a cocktail of TNF-α + IFN-γ + IL-6, increased expression of ACE2/DPP4, accentuated the pro-inflammatory senescence-associated secretory phenotype (SASP), and decreased cellular proliferative capacity, consistent with progression towards a cellular senescence-like state. IL-6 by itself failed to induce substantial effects on viral entry receptors or SASP-related genes, while synergy between TNF-α and IFN-γ initiated a positive feedback loop via hyper-activation of the JAK/STAT1 pathway, causing SASP amplification. Breaking the interactive loop between senescence and cytokine secretion with JAK inhibitor ruxolitinib or antiviral drug remdesivir prevented hyper-inflammation, normalized SARS-CoV-2 entry receptor expression, and restored HUVECs proliferative capacity. This loop appears to underlie cytokine-mediated viral entry receptor activation and links with senescence and hyper-inflammation.
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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.