ArticleNature communications2023
Dimethyl fumarate and 4-octyl itaconate are anticoagulants that suppress Tissue Factor in macrophages via inhibition of Type I Interferon.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 62 citations in OpenAlex.
- Metabolic control of macrophages in coronavirus disease 2019.Virulence · 2026Review
- Itaconation and Succination as Metabolite-Derived Cysteine Modifications in Inflammatory Signalling: Biochemical Mechanisms, Chemoproteomic Mapping, and Therapeutic Opportunities.Cell biochemistry and biophysics · 2026Review
- Itaconate metabolism in regulated cell death.Molecular and cellular biochemistry · 2026Review
- Cell-Surface Signatures and Targets of Modulated Vascular Smooth Muscle Cells in Atherosclerosis: From State Identification to Precision Intervention.Journal of cardiovascular development and disease · 2026Review
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Neutrophil extracellular traps in thrombosis of hematologic malignancies: Underlying mechanisms and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- Offense and defense: itaconate mediates bidirectional immune regulation of host-bacteria interaction.Journal of biomedical science · 2026Review
- Itaconate modifications: Mechanisms and applications.Journal of intensive medicine · 2026Review
- Machine learning integration of bulk and single-cell RNA-Seq data reveals COPS2 as a central immune regulator in deep vein thrombosis.American journal of translational research · 2026Article
- Tissue factor detection in mouse tissues by western blotting using commercial antibodies.Research and practice in thrombosis and haemostasis · 2026Article
- Crosstalk of mitochondrial dysfunction and macrophage polarization in sepsis.Frontiers in immunology · 2026Review
- Gut-Brain Axis Dysregulation in Inflammatory Bowel Disease: Implications for Coagulation Abnormalities and Extraintestinal Manifestations.International journal of general medicine · 2026Review
- Dimethyl itaconate suppresses dendritic cell and CD8BMC medicine · 2025Article
- Intelligent responsive PVA hydrogel loaded with composite MXene nanozyme enables efficient myocardial infarction repair by disrupting the oxidative stress-inflammation cascade.Materials today. Bio · 2025Article
- Epigenetic metabolite lipid nanoparticles alleviate venous thrombosis via bone marrow reprogramming.Blood vessels, thrombosis & hemostasis · 2025Article
- Dimethyl fumarate improves sepsis-induced acute lung injury by inhibiting STING-mediated ferroptosis.Journal of bioenergetics and biomembranes · 2025Article
- Fumarate Signaling in Cardiovascular Disease: Therapeutic Potential and Pathologic Pitfalls of DMF/MMF and FH1 Deficiency.Journal of cardiovascular translational research · 2025Review
- Reprogramming immunity with itaconate: metabolic mechanisms and therapeutic perspectives.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Pharmacological inhibition of STING-mediated GPX4 autophagic degradation by 4-octyl itaconate ameliorates sepsis-induced acute kidney injury.Apoptosis : an international journal on programmed cell death · 2025Article
- Itaconate modulates immune responses via inhibition of peroxiredoxin 5.Nature metabolism · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
36 authors at 6 institutions in 4 countries.
Funding
Abstract
Excessive inflammation-associated coagulation is a feature of infectious diseases, occurring in such conditions as bacterial sepsis and COVID-19. It can lead to disseminated intravascular coagulation, one of the leading causes of mortality worldwide. Recently, type I interferon (IFN) signaling has been shown to be required for tissue factor (TF; gene name F3) release from macrophages, a critical initiator of coagulation, providing an important mechanistic link between innate immunity and coagulation. The mechanism of release involves type I IFN-induced caspase-11 which promotes macrophage pyroptosis. Here we find that F3 is a type I IFN-stimulated gene. Furthermore, F3 induction by lipopolysaccharide (LPS) is inhibited by the anti-inflammatory agents dimethyl fumarate (DMF) and 4-octyl itaconate (4-OI). Mechanistically, inhibition of F3 by DMF and 4-OI involves suppression of Ifnb1 expression. Additionally, they block type I IFN- and caspase-11-mediated macrophage pyroptosis, and subsequent TF release. Thereby, DMF and 4-OI inhibit TF-dependent thrombin generation. In vivo, DMF and 4-OI suppress TF-dependent thrombin generation, pulmonary thromboinflammation, and lethality induced by LPS, E. coli, and S. aureus, with 4-OI additionally attenuating inflammation-associated coagulation in a model of SARS-CoV-2 infection. Our results identify the clinically approved drug DMF and the pre-clinical tool compound 4-OI as anticoagulants that inhibit TF-mediated coagulopathy via inhibition of the macrophage type I IFN-TF axis.
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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.