ArticleAmerican journal of respiratory cell and molecular biology2013
α₁-Antitrypsin modulates lung endothelial cell inflammatory responses to TNF-α.
Article in American journal of respiratory cell and molecular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07125664 (A Two-center, Randomized, Double-blind, Placebo-controlled Study of Intravenous Plasma-purified Alpha-1 Antitrypsin for Hospitalized Patients With COPD Exacerbations), which is not on this map. Cited by 45 papers.
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.
A Two-center, Randomized, Double-blind, Placebo-controlled Study of Intravenous Plasma-purified Alpha-1 Antitrypsin for Hospitalized Patients With COPD Exacerbations (AECOPD Study)
Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- The Biological Effects of Double-Dose Alpha-1 Antitrypsin Augmentation Therapy. A Pilot Clinical Trial.American journal of respiratory and critical care medicine · 2019Trial
- Polymerized Z-α-1 antitrypsin leads to lung injury in a murine model of emphysema.JCI insight · 2026Article
- Alpha-1 antitrypsin as a new biomarker of inflammation, infection and disease severity in community-acquired pneumonia: a prospective cohort study.Scientific reports · 2026Article
- Alpha-1 antitrypsin-glucocorticoid receptor axis: a new pathway in immune modulation.Molecular medicine (Cambridge, Mass.) · 2026Article
- Urinary Peptidomic Profiling In Post-Acute Sequelae of SARS-CoV-2 Infection: A Case-Control Study.Proteomics · 2026Article
- Protein Fragments: From Biomarkers to Therapeutic Targets-A Focus on α1-Antitrypsin-Derived Peptides.Mediators of inflammation · 2026Review
- Piezo1 aggravates ischemia/reperfusion-induced acute kidney injury by CaRenal failure · 2025Article
- Clinical Study Support by Long-Term Stability Studies of AlphaPharmaceuticals (Basel, Switzerland) · 2025Article
- α‑1 Antitrypsin is a potential target of inflammation and immunomodulation (Review).Molecular medicine reports · 2025Review
- The Inhibitory Effects of Alpha 1 Antitrypsin on Endosomal TLR Signaling Pathways.Biomolecules · 2025Article
- Article
- Alpha1-antitrypsin improves survival in murine abdominal sepsis model by decreasing inflammation and sequestration of free heme.Frontiers in immunology · 2024Article
- Alpha-1 antitrypsin inhibits fractalkine-mediated monocyte-lung endothelial cell interactions.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- NAFLD and AATD Are Two Diseases with Unbalanced Lipid Metabolism: Similarities and Differences.Biomedicines · 2023Review
- Type 1 diabetes contributes to combined pulmonary fibrosis and emphysema in male alpha 1 antitrypsin deficient mice.PloS one · 2023Article
- Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution.Theranostics · 2023Article
- Article
- A Review of Alpha-1 Antitrypsin Binding Partners for Immune Regulation and Potential Therapeutic Application.International journal of molecular sciences · 2022Review
- Role of endothelial cells in graft-versus-host disease.Frontiers in immunology · 2022Review
- Protease-Specific Biomarkers to Analyse Protease Inhibitors for Emphysema Associated with Alpha 1-Antitrypsin Deficiency. An Overview of Current Approaches.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
α₁-Antitrypsin (A1AT) is an acute-phase reactant, but also a major protective factor against the development of chronic obstructive pulmonary disease, a complex disease with sustained chronic inflammation. The lung-protective effects of A1AT have been attributed to the inhibition of proteases involved in lung matrix fragmentation, macrophage activation, and endothelial-cell apoptosis. More recently, A1AT has been shown to directly interact with or modulate the actions of cytokines such as TNF-α or IL-1 in inflammatory cells, but its effect on the lung endothelium, an active participant in the amplification and resolution of inflammation, has received little attention. An important role of A1AT in modulating lung endothelial inflammatory responses is expected, given the high concentrations of circulating A1AT during inflammation and its active uptake by endothelial cells. We investigated the role of A1AT in primary lung microvascular endothelial cell activation by relevant cytokines such as TNF-α or IL-1β. Despite an initial marked augmentation of TNF-α self-induced transcription, A1AT inhibited TNF-α receptor 1 up-regulation and significantly reduced TNF-α secretion, effects that were associated with inhibition of TNF-α-converting enzyme activity. Furthermore, A1AT inhibited calpain activity, whose activation by TNF-α contributed to decreased intracellular A1AT concentrations. These data indicate that A1AT initially facilitates acute responses of the endothelium to TNF-α, followed by selective inhibition of TNF-α-induced-self amplification, which may assist the vasculature in the resolution of chronic 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.