ArticleAmerican journal of respiratory cell and molecular biology2009
Leukocyte elastase induces lung epithelial apoptosis via a PAR-1-, NF-kappaB-, and p53-dependent pathway.
Article in American journal of respiratory cell and molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 67 citations in OpenAlex.
- MLKL regulates intracellular trafficking of neutrophil elastase to promote lung epithelial cell senescence.American journal of respiratory cell and molecular biology · 2026Article
- Research progress on the mechanism of curcumin in cerebral ischemia/reperfusion injury: a narrative review.Apoptosis : an international journal on programmed cell death · 2023Review
- The Yin and Yang of Pneumolysin During Pneumococcal Infection.Frontiers in immunology · 2022Review
- Neutrophil Extracellular Traps (NETs) in Severe SARS-CoV-2 Lung Disease.International journal of molecular sciences · 2021Review
- Proteases, Mucus, and Mucosal Immunity in Chronic Lung Disease.International journal of molecular sciences · 2021Review
- Pathophysiology of Lung Disease and Wound Repair in Cystic Fibrosis.Pathophysiology : the official journal of the International Society for Pathophysiology · 2021Review
- Sterile inflammation in thoracic transplantation.Cellular and molecular life sciences : CMLS · 2021Review
- Inflammation Profiling of Critically Ill Coronavirus Disease 2019 Patients.Critical care explorations · 2020Article
- Targeting neutrophil extracellular traps in severe acute pancreatitis treatment.Therapeutic advances in gastroenterology · 2020Review
- Glycosaminoglycans as Multifunctional Anti-Elastase and Anti-Inflammatory Drugs in Cystic Fibrosis Lung Disease.Frontiers in pharmacology · 2020Review
- TRPV4-A Missing Link Between Mechanosensation and Immunity.Frontiers in immunology · 2020Review
- Protease-activated receptor-1 impedes prostate and intestinal tumor progression in mice.Journal of thrombosis and haemostasis : JTH · 2018Article
- Protease-activated receptor 1 activation enhances doxorubicin-induced cardiotoxicity.Journal of molecular and cellular cardiology · 2018Article
- New Insights into the Immune Molecular Regulation of the Pathogenesis of Acute Respiratory Distress Syndrome.International journal of molecular sciences · 2018Review
- Report of the ISHLT Working Group on Primary Lung Graft Dysfunction Part III: Mechanisms: A 2016 Consensus Group Statement of the International Society for Heart and Lung Transplantation.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2017Review
- Exogenous neutrophil elastase enters bronchial epithelial cells and suppresses cigarette smoke extract-induced heme oxygenase-1 by cleaving sirtuin 1.The Journal of biological chemistry · 2017Article
- With Friends Like These: The Complex Role of Neutrophils in the Progression of Severe Pneumonia.Frontiers in cellular and infection microbiology · 2017Review
- Neutrophil-Epithelial Interactions: A Double-Edged Sword.The American journal of pathology · 2016Review
- Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation.Scientific reports · 2016Article
- Roles of PAR1 and PAR2 in viral myocarditis.Thrombosis research · 2014Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Leukocyte elastase induces apoptosis of lung epithelial cells via alterations in mitochondrial permeability, but the signaling pathways regulating this response remain uncertain. Here we investigated the involvement of proteinase-activated receptor-1 (PAR-1), the transcription factor NF-kappaB, and the protooncogene p53 in this pathway. Elastase-induced apoptosis of lung epithelial cells correlated temporally with activation of NF-kappaB, phosphorylation, and nuclear translocation of p53, increased p53 up-regulated modulator of apoptosis (PUMA) expression, and mitochondrial translocation of Bax resulting in enhanced permeability. Elastase-induced apoptosis was also prevented by pharmacologic inhibitors of NF-kappaB and p53 and by short interfering RNA knockdown of PAR-1, p53, or PUMA. These inhibitors prevented elastase-induced PUMA expression, mitochondrial translocation of Bax, increased mitochondrial permeability, and attenuated apoptosis. NF-kappaB inhibitors also reduced p53 phosphorylation. We conclude that elastase-induced apoptosis of lung epithelial cells is mediated by a PAR-1-triggered pathway involving activation of NF-kappaB and p53, and a PUMA- and Bax-dependent increase in mitochondrial permeability leading to activation of distal caspases. Further, p53 contributes to elastase-induced apoptosis by both transcriptional and post-transcriptional mechanisms.
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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.