ArticleJournal of immunology (Baltimore, Md. : 1950)2013
TNF-induced death signaling triggers alveolar epithelial dysfunction in acute lung injury.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- Mesenchymal stem cell therapy for paraquat poisoning: A systematic review and meta-analysis of preclinical studies.PloS one · 2018Pooled it
- A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study.European journal of anaesthesiology · 2020Trial
- Trial
- Beyond Acute Infection: A Conceptual Framework Linking Zoonotic Bacterial Pathogens to Pulmonary Fibrosis and Lung Carcinogenesis.Biomedicines · 2026Review
- Therapeutic and prophylactic roles of oleuropein in experimental acute lung injury: Modulation of tumor necrosis factor-α and nuclear factor erythroid 2-related factor 2 pathways.Experimental and therapeutic medicine · 2026Article
- Diffuse alveolar damage, acute respiratory distress syndrome (ARDS), and non-cardiogenic pulmonary edema (NCPE). Part 2: NCPE apart from ARDS, molecular and cellular consequences of primary injury to the lung interstitium, with comparative immunology of the dog and cat.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2026Review
- Regenerative therapeutics for chronic obstructive pulmonary disease.Pharmacological reviews · 2026Review
- The Anti-Inflammatory Role of GLP-1 RAs in Acute Lung Injury and Acute Respiratory Distress Syndrome.International journal of molecular sciences · 2026Review
- Comparative Immunomodulatory Efficacy of Secukinumab and Honokiol in Experimental Asthma and Acute Lung Injury.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The immune receptors TLR4 and SLAMF1 regulate TNF release by human metapneumovirus in human macrophages.Frontiers in immunology · 2025Article
- IFN Receptor 2 Regulates TNF-α-Mediated Damaging Inflammation during Aspergillus Pulmonary Infection.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- A narrative review of chemokine receptors CXCR1 and CXCR2 and their role in acute respiratory distress syndrome.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Capsaicin Attenuates LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Autophagy Through Regulation of the TRPV1/AKT Pathway.Journal of inflammation research · 2024Article
- Levocetrizine attenuates cyclophosphamide-induced lung injury through inhibition of TNF-α, IL-1β, TGF-β and MMP-9.BMC pharmacology & toxicology · 2023Article
- hWJMSCs inhibit inflammation and apoptosis in an ARDS cell model.Journal of Taibah University Medical Sciences · 2023Article
- Age-related changes in plasma biomarkers and their association with mortality in COVID-19.The European respiratory journal · 2023Article
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Drug Cocktail Formulation via Circuit Design.IEEE transactions on molecular, biological, and multi-scale communications · 2023Article
- Oxidative Stress and Inflammation in Acute and Chronic Lung Injuries.Antioxidants (Basel, Switzerland) · 2023Review
- Activation of Endothelial Large Conductance Potassium Channels Protects against TNF-α-Induced Inflammation.International journal of molecular sciences · 2023Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The ability of the alveolar epithelium to prevent and resolve pulmonary edema is a crucial determinant of morbidity and mortality in acute lung injury (ALI). TNF has been implicated in ALI pathogenesis, but the precise mechanisms remain undetermined. We evaluated the role of TNF signaling in pulmonary edema formation in a clinically relevant mouse model of ALI induced by acid aspiration and investigated the effects of TNF p55 receptor deletion, caspase-8 inhibition, and alveolar macrophage depletion on alveolar epithelial function. We found that TNF plays a central role in the development of pulmonary edema in ALI through activation of p55-mediated death signaling, rather than through previously well-characterized p55-mediated proinflammatory signaling. Acid aspiration produced pulmonary edema with significant alveolar epithelial dysfunction, as determined by alveolar fluid clearance (AFC) and intra-alveolar levels of the receptor for advanced glycation end-products. The impairment of AFC was strongly correlated with lung caspase-8 activation, which was localized to type 1 alveolar epithelial cells by flow cytometric analysis. p55-deficient mice displayed markedly attenuated injury, with improved AFC and reduced caspase-8 activity but no differences in downstream cytokine/chemokine production and neutrophil recruitment. Caspase-8 inhibition significantly improved AFC and oxygenation, whereas depletion of alveolar macrophages attenuated epithelial dysfunction with reduced TNF production and caspase-8 activity. These results provide in vivo evidence for a novel role for TNF p55 receptor-mediated caspase-8 signaling, without substantial apoptotic cell death, in triggering alveolar epithelial dysfunction and determining the early pathophysiology of ALI. Blockade of TNF-induced death signaling may provide an effective early-phase strategy for ALI.
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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.