ArticleAmerican journal of respiratory cell and molecular biology2015
Statin-conferred enhanced cellular resistance against bacterial pore-forming toxins in airway epithelial cells.
Article in American journal of respiratory cell and molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Pneumolysin as a target for new therapies against pneumococcal infections: A systematic review.PloS one · 2023Pooled it
- Impact of Long-Term Statin Therapy on Incidence and Severity of Community-Acquired Pneumonia: A Real-World Data Analysis.Biomedicines · 2025Article
- Story of Pore-Forming Proteins from Deadly Disease-Causing Agents to Modern Applications with Evolutionary Significance.Molecular biotechnology · 2024Review
- Statin Use and Reduced Risk of Pneumonia in Patients with Melioidosis: A Lung-Specific Statin Association.Annals of the American Thoracic Society · 2024Article
- Repositioning of HMG-CoA Reductase Inhibitors as Adjuvants in the Modulation of Efflux Pump-Mediated Bacterial and Tumor Resistance.Antibiotics (Basel, Switzerland) · 2023Review
- Glucocorticoids increase tissue cell protection against pore-forming toxins from pathogenic bacteria.Communications biology · 2023Article
- Article
- Role of toll-like receptors and nod-like receptors in acute lung infection.Frontiers in immunology · 2023Review
- Membrane Cholesterol Content and Lipid Organization Influence Melittin and Pneumolysin Pore-Forming Activity.Toxins · 2022Article
- The Yin and Yang of Pneumolysin During Pneumococcal Infection.Frontiers in immunology · 2022Review
- Oxysterols Protect Epithelial Cells Against Pore-Forming Toxins.Frontiers in immunology · 2022Article
- Oxysterols protect bovine endometrial cells against pore-forming toxins from pathogenic bacteria.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Bisphosphonate inhibitors of squalene synthase protect cells against cholesterol-dependent cytolysins.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Pneumolysin: Pathogenesis and Therapeutic Target.Frontiers in microbiology · 2020Review
- Inhibition of Pore-Forming Proteins.Toxins · 2019Review
- Statins improve the long-term prognosis in patients who have survived sepsis: A nationwide cohort study in Taiwan (STROBE complaint).Medicine · 2019Observational
- Statins influence epithelial expression of the anti-microbial peptide LL-37/hCAP-18 independently of the mevalonate pathway.Clinical and experimental immunology · 2019Article
- Pharmacological Targeting of Pore-Forming Toxins as Adjunctive Therapy for Invasive Bacterial Infection.Toxins · 2018Review
- Statin for Tuberculosis and Pneumonia in Patients with Asthma⁻Chronic Pulmonary Disease Overlap Syndrome: A Time-Dependent Population-Based Cohort Study.Journal of clinical medicine · 2018Article
- Isoprenoids increase bovine endometrial stromal cell tolerance to the cholesterol-dependent cytolysin from Trueperella pyogenes.Biology of reproduction · 2018Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Statins are widely used to prevent cardiovascular disease. In addition to their inhibitory effects on cholesterol synthesis, statins have beneficial effects in patients with sepsis and pneumonia, although molecular mechanisms have mostly remained unclear. Using human airway epithelial cells as a proper in vitro model, we show that prior exposure to physiological nanomolar serum concentrations of simvastatin (ranging from 10-1,000 nM) confers significant cellular resistance to the cytotoxicity of pneumolysin, a pore-forming toxin and the main virulence factor of Streptococcus pneumoniae. This protection could be demonstrated with a different statin, pravastatin, or on a different toxin, α-hemolysin. Furthermore, through the use of gene silencing, pharmacological inhibitors, immunofluorescence microscopy, and biochemical and metabolic rescue approaches, we demonstrate that the mechanism of protection conferred by simvastatin at physiological nanomolar concentrations could be different from the canonical mevalonate pathways seen in most other mechanistic studies conducted with statins at micromolar levels. All of these data are integrated into a protein synthesis-dependent, calcium-dependent model showing the interconnected pathways used by statins in airway epithelial cells to elicit an increased resistance to pore-forming toxins. This research fills large gaps in our understanding of how statins may confer host cellular protection against bacterial infections in the context of airway epithelial cells without the confounding effect from the presence of immune cells. In addition, our discovery could be potentially developed into a host-centric strategy for the adjuvant treatment of pore-forming toxin associated bacterial infections.
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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.