Trial reportRespiratory research2016
Simvastatin up-regulates adenosine deaminase and suppresses osteopontin expression in COPD patients through an IL-13-dependent mechanism.
Trial report in Respiratory research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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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
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Association of the IL-13 polymorphisms rs1800925 and rs20541 with chronic obstructive pulmonary disease risk: An updated meta-analysis.Medicine · 2017Pooled it
- The Mediation of Circulating Inflammatory Proteins in the Causal Pathway from Immune Cells to COPD.International journal of chronic obstructive pulmonary disease · 2025Article
- IL-13 induces loss of CFTR in ionocytes and reduces airway epithelial fluid absorption.The Journal of clinical investigation · 2024Article
- CXCL9, IL2RB, and SPP1, potential diagnostic biomarkers in the co-morbidity pattern of atherosclerosis and non-alcoholic steatohepatitis.Scientific reports · 2024Article
- Role of osteopontin in cancer development and treatment.Heliyon · 2023Review
- Advanced Biomarkers of Hepatotoxicity in Psychiatry: A Narrative Review and Recommendations for New Psychoactive Substances.International journal of molecular sciences · 2023Review
- Osteopontin and Regulatory T Cells in Effector Phase of Allergic Contact Dermatitis.Journal of clinical medicine · 2023Article
- Pleotropic effects of statins: the dilemma of wider utilization of statin.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2023Review
- The impact of statin use before intensive care unit admission on patients with acute kidney injury after cardiac surgery.Frontiers in pharmacology · 2023Article
- Effect of Cigarette Smoke on Gut Microbiota: State of Knowledge.Frontiers in physiology · 2021Review
- Estimation of Hub Genes and Infiltrating Immune Cells in Non-Smoking Females with Lung Adenocarcinoma by Integrated Bioinformatic Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- IRF4 and STAT3 activities are associated with the imbalanced differentiation of T-cells in responses to inhalable particulate matters.Respiratory research · 2020Article
- Review
- Statins versus placebo for people with chronic obstructive pulmonary disease.The Cochrane database of systematic reviews · 2019Review
- Sustained adenosine exposure causes endothelial mitochondrial dysfunction via equilibrative nucleoside transporters.Pulmonary circulationArticle
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAdenosine deaminase (ADA) and osteopontin (OPN) may play opposing roles in the pathogenesis of COPD. Deficiency of ADA results in enhanced adenosine signaling which up-regulates OPN expression. Although statins suppress OPN in cancer cells, little is known about their effects on ADA and OPN in COPD patients.
methodsWe extended a previous randomized double-blind placebo crossover study to investigate the effects of simvastatin (20 mg/day) on sputum ADA and OPN expression and explored the underlying signaling pathways involved by conducting in vitro experiments with cigarette smoke extract (CSE)-treated monocyte-derived macrophages (MDM) from COPD patients and healthy subjects.
resultsSimvastatin decreased sputum IL-13, OPN and CD73, while increasing ADA expression, irrespective of inhaled corticosteroid treatment and smoking status in parallel to increased inosine levels. The degree of simvastatin-restored ADA activity was significantly correlated with the magnitude of changes in pre-bronchodilator FEV1. Mechanistic exploration showed that CSE enhanced the expression of IL-13, which induced an increase in OPN and inhibited ADA mRNA accumulation in MDM from COPD patients but not healthy subjects through a STAT6-dependent mechanism. Simvastatin treatment inhibited IL-13 transcription in a dose-dependent manner, and therefore diminished the IL-13-induced increase in OPN and restored IL-13-suppressed ADA. There was no effect of simvastatin on adenosine receptors in CSE-stimulated MDM, indicating that its effects were on the adenosine pathway.
conclusionSimvastatin reversed IL-13-suppressed ADA activity that leads to the down-regulation of adenosine signaling and therefore inhibits OPN expression through the direct inhibition of IL-13-activated STAT6 pathway. Inhibition of IL-13 may reverse the imbalance between ADA and OPN in COPD and therefore may prevent COPD progression.
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