ArticleJournal of immunology (Baltimore, Md. : 1950)2022
α1-Antitrypsin Binds to the Glucocorticoid Receptor with Anti-Inflammatory and Antimycobacterial Significance in Macrophages.
Article in Journal of immunology (Baltimore, Md. : 1950), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
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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
16 citing papers in PubMed, 17 citations in OpenAlex.
- Alpha-1 antitrypsin-glucocorticoid receptor axis: a new pathway in immune modulation.Molecular medicine (Cambridge, Mass.) · 2026Article
- The Role of Alpha-1 Antitrypsin in the Pathophysiology and Treatment of Inflammatory Lung Diseases.Journal of inflammation research · 2026Review
- Alpha-1 Antitrypsin Mediates Spontaneous Resolution of Acute Gouty Inflammation Via Inhibiting Caspase 3/GSDME-dependent Macrophage Pyroptosis.Inflammation · 2025Article
- Plasma lipopolysaccharide levels predict mortality in acutely ill children in Low- and Middle-Income Countries.Nature communications · 2025Article
- SERPINA1 gene regulates the tumorigenesis and progression of breast cancer through PI3K/AKT signaling pathway and tumor immune microenvironment.Scientific reports · 2025Article
- Resolution Pharmacology: State-of-the-art and therapeutic landscape.Pharmacological reviews · 2025Review
- Dexamethasone inhibits Mycobacterium tuberculosis-induced glycolysis but preserves antimicrobial function in primary human macrophages.Scientific reports · 2025Article
- Bioinformatic analysis of serpina1 expression in papillary thyroid carcinoma and its potential association with Hashimoto's thyroiditis.Discover oncology · 2025Article
- Review
- Alpha-1-antitrypsin improves anastomotic healing in intestinal epithelial cells model.Pediatric surgery international · 2024Article
- Analysis of alpha-1-antitrypsin (AAT)-regulated, glucocorticoid receptor-dependent genes in macrophages reveals a novel host defense function of AAT.Physiological reports · 2024Article
- RNA sequencing and proteomic profiling reveal alterations by MPTP in chronic stomach mucosal injury in tree shrew Chinese (Tupaia belangeri chinensis).Scientific reports · 2024Article
- Modulating glucocorticoid receptor actions in physiology and pathology: Insights from coregulators.Pharmacology & therapeutics · 2023Review
- Serpin Family A Member 1 Is Prognostic and Involved in Immunological Regulation in Human Cancers.International journal of molecular sciences · 2023Article
- Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence.Biochemical Society transactions · 2023Review
- Humoral Innate Immunity and Acute-Phase Proteins.The New England journal of medicine · 2023Review
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 5 countries.
Funding
Abstract
α1-Antitrypsin (AAT), a serine protease inhibitor, is the third most abundant protein in plasma. Although the best-known function of AAT is irreversible inhibition of elastase, AAT is an acute-phase reactant and is increasingly recognized to have a panoply of other functions, including as an anti-inflammatory mediator and a host-protective molecule against various pathogens. Although a canonical receptor for AAT has not been identified, AAT can be internalized into the cytoplasm and is known to affect gene regulation. Because AAT has anti-inflammatory properties, we examined whether AAT binds the cytoplasmic glucocorticoid receptor (GR) in human macrophages. We report the finding that AAT binds to GR using several approaches, including coimmunoprecipitation, mass spectrometry, and microscale thermophoresis. We also performed in silico molecular modeling and found that binding between AAT and GR has a plausible stereochemical basis. The significance of this interaction in macrophages is evinced by AAT inhibition of LPS-induced NF-κB activation and IL-8 production as well as AAT induction of angiopoietin-like 4 protein, which are, in part, dependent on GR. Furthermore, this AAT-GR interaction contributes to a host-protective role against mycobacteria in macrophages. In summary, this study identifies a new mechanism for the gene regulation, anti-inflammatory, and host-defense properties of AAT.
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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.