ArticleAmerican journal of respiratory cell and molecular biology2005
Proteinase-activated receptor-1 mediates elastase-induced apoptosis of human lung epithelial cells.
Article in American journal of respiratory cell and molecular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 131 citations in OpenAlex.
- Neutrophilic inflammation in bronchiectasis.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Loss of CFTR Reverses Senescence Hallmarks in SARS-CoV-2 Infected Bronchial Epithelial Cells.International journal of molecular sciences · 2024Article
- Mitochondria in health, disease, and aging.Physiological reviews · 2023Review
- Dipeptidyl peptidase 1 inhibition as a potential therapeutic approach in neutrophil-mediated inflammatory disease.Frontiers in immunology · 2023Review
- Pregnancy-specific expression of protease-activated receptor 1: a therapeutic target for prevention and treatment of preeclampsia?American journal of obstetrics and gynecology · 2022Review
- Alpha-1 antitrypsin limits neutrophil extracellular trap disruption of airway epithelial barrier function.Frontiers in immunology · 2022Article
- Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection.Biochemistry (Moscow) Supplement. Series B, Biomedical chemistry · 2022Article
- Mechanisms underlying unidirectional laminar shear stress-mediated Nrf2 activation in endothelial cells: Amplification of low shear stress signaling by primary cilia.Redox biology · 2021Review
- Neutrophil Elastase and Chronic Lung Disease.Biomolecules · 2021Review
- The Road to Low-Dose Aspirin Therapy for the Prevention of Preeclampsia Began with the Placenta.International journal of molecular sciences · 2021Review
- Protease-Activated Receptor-1 Antagonist Protects Against Lung Ischemia/Reperfusion Injury.Frontiers in pharmacology · 2021Article
- Proteases Activate Pregnancy Neutrophils by a Protease-Activated Receptor 1 Pathway: Epigenetic Implications for Preeclampsia.Reproductive sciences (Thousand Oaks, Calif.) · 2020Article
- Proteinase-activated receptor 1: A target for repurposing in the treatment of COVID-19?British journal of pharmacology · 2020Article
- LJ-2698, an Adenosine A3 Receptor Antagonist, Alleviates Elastase-Induced Pulmonary Emphysema in Mice.Biomolecules & therapeutics · 2020Article
- Protease Amplification of the Inflammatory Response Induced by Commensal Bacteria: Implications for Racial Disparity in Term and Preterm Birth.Reproductive sciences (Thousand Oaks, Calif.) · 2020Article
- Cell Death in the Lung: The Apoptosis-Necroptosis Axis.Annual review of physiology · 2019Review
- Matrix Metalloprotease-1 and Elastase Are Novel Uterotonic Agents Acting Through Protease-Activated Receptor 1.Reproductive sciences (Thousand Oaks, Calif.) · 2018Article
- Mechanisms and treatment of organ failure in sepsis.Nature reviews. Nephrology · 2018Review
- Sarsasapogenin-AA13 inhibits LPS-induced inflammatory responses in macrophage cells in vitro and relieves dimethylbenzene-induced ear edema in mice.Acta pharmacologica Sinica · 2017Article
- PlGF mediates neutrophil elastase-induced airway epithelial cell apoptosis and emphysema.Respiratory research · 2014Article
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12 authors at 1 institution in 2 countries.
Funding
Abstract
Apoptosis of distal lung epithelial cells plays a pivotal role in the pathogenesis of acute lung injury. In this context, proteinases, either circulating or leukocyte-derived, may contribute to epithelial apoptosis and lung injury. We hypothesized that apoptosis of lung epithelial cells induced by leukocyte elastase is mediated via the proteinase activated receptor (PAR)-1. Leukocyte elastase, thrombin, and PAR-1-activating peptide, but not the control peptide, induced apoptosis in human airway and alveolar epithelial cells as assessed by increases in cytoplasmic histone-associated DNA fragments and TUNEL staining. These effects were largely prevented by a specific PAR-1 antagonist and by short interfering RNA directed against PAR-1. To ascertain the mechanism of epithelial apoptosis, we determined that PAR-1AP, thrombin, and leukocyte elastase dissipated mitochondrial membrane potential, induced translocation of cytochrome c to the cytosol, enhanced cleavage of caspase-9 and caspase-3, and led to JNK activation and Akt inhibition. In concert, these observations provide strong evidence that leukocyte elastase mediates apoptosis of human lung epithelial cells through PAR-1-dependent modulation of the intrinsic apoptotic pathway via alterations in mitochondrial permeability and by modulation of JNK and Akt.
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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.