ArticlePloS one2015
In-vitro suppression of IL-6 and IL-8 release from human pulmonary epithelial cells by non-anticoagulant fraction of enoxaparin.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
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- Acute upper limb arterial ischemia in patients diagnosed with COVID-19: case series.Jornal vascular brasileiro · 2021Article
- Article
- Enoxaparin Attenuates Acute Lung Injury and Inflammasome Activation after Traumatic Brain Injury.Journal of neurotrauma · 2021Article
- Impact of low molecular weight heparin administration on the clinical course of the COVID-19 diseaseTurkish journal of medical sciences · 2021Article
- Antithrombotic and Anti-Inflammatory Effects of Fondaparinux and Enoxaparin in Hospitalized COVID-19 Patients: The FONDENOXAVID Study.Journal of blood medicine · 2021Article
- The Use of the Anticoagulant Heparin and Corticosteroid Dexamethasone as Prominent Treatments for COVID-19.Frontiers in medicine · 2021Review
- Mechanisms of COVID-19 thrombosis in an inflammatory environment and new anticoagulant targets.American journal of translational research · 2021Review
- Acute limb ischemia in patients with COVID-19 pneumonia.Journal of vascular surgery · 2020Observational
- A lesson from a saboteur: High-MW kininogen impact in coronavirus-induced disease 2019.British journal of pharmacology · 2020Review
- Pulmonary involvement in systemic sclerosis: exploring cellular, genetic and epigenetic mechanisms.Rheumatology international · 2020Review
- Beneficial non-anticoagulant mechanisms underlying heparin treatment of COVID-19 patients.EBioMedicine · 2020Review
- Use of Enoxaparin to Counteract COVID-19 Infection and Reduce Thromboembolic Venous Complications: A Review of the Current Evidence.Frontiers in pharmacology · 2020Review
- The Potential Role of Heparin in Patients With COVID-19: Beyond the Anticoagulant Effect. A Review.Frontiers in pharmacology · 2020Review
- Comparison of the Effects of Fucoidans on the Cell Viability of Tumor and Non-Tumor Cell Lines.Marine drugs · 2019Article
- Cellular and Molecular Effects of High-Molecular-Weight Heparin on Matrix Metalloproteinase 9 Expression.International journal of molecular sciences · 2019Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEnoxaparin, a mixture of anticoagulant and non-anticoagulant fractions, is widely used as an anticoagulant agent. However, it is also reported to possess anti-inflammatory properties. Our study indicated that enoxaparin inhibits the release of IL-6 and IL-8 from A549 pulmonary epithelial cells. Their release causes extensive lung tissue damage. The use of enoxaparin as an anti-inflammatory agent is hampered due to the risk of bleeding associated with its anticoagulant fractions. Therefore, we aimed to identify the fraction responsible for the observed anti-inflammatory effect of enoxaparin and to determine the relationship between its structure and biological activities.
methodsA549 pulmonary epithelial cells were pre-treated in the presence of enoxaparin and its fractions. The levels of IL-6 and IL-8 released from the trypsin-stimulated cells were measured by ELISA. The anticoagulant activity of the fraction responsible for the effect of enoxaparin was determined using an anti-factor-Xa assay. The fraction was structurally characterised using nuclear magnetic resonance. The fraction was 2-O, 6-O or N-desulfated to determine the position of sulfate groups required for the inhibition of interleukins. High-performance size-exclusion chromatography was performed to rule out that the observed effect was due to the interaction between the fraction and trypsin or interleukins.
resultsEnoxaparin (60 μg/mL) inhibited the release of IL-6 and IL-8 by >30%. The fraction responsible for this effect of enoxaparin was found to be a disaccharide composed of α-L-iduronic-acid and α-D-glucosamine-6-sulfate. It (15 μg/mL) inhibited the release of interleukins by >70%. The 6-O sulphate groups were responsible for its anti-inflammatory effect. The fraction did not bind to trypsin or interleukins, suggesting the effect was not due to an artefact of the experimental model.
conclusionThe identified disaccharide has no anticoagulant activity and therefore eliminates the risk of bleeding associated with enoxaparin. Future in-vivo studies should be designed to validate findings of the current study.
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