ArticleFrontiers in immunology2022
Itaconate Suppresses Formation of Neutrophil Extracellular Traps (NETs): Involvement of Hypoxia-Inducible Factor 1α (Hif-1α) and Heme Oxygenase (HO-1).
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Neutrophil extracellular traps in cardiovascular disease: Mechanisms and therapeutic implications (Review).International journal of molecular medicine · 2026Review
- Itaconate alleviates LPS-induced septic liver injury by regulating ROS-PAD4-mediated macrophages extracellular traps through Nrf2.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Role of itaconate in intestinal disease (Review).International journal of molecular medicine · 2026Review
- Fumarate inhibits the formation of neutrophil extracellular traps (NETs) in a Nrf2-controlled and Annexin-A1-dependent manner associated with mitochondrial fusion.Frontiers in immunology · 2026Article
- One trigger, two fates: hemolysate shapes neutrophil extracellular traps (NETs) formation in a context-dependent manner.Frontiers in immunology · 2026Article
- Inhibition of Macrophage ARID3A Alleviates Myocardial Ischemia-Reperfusion Injury After Heart Transplantation by Reducing THBS1/CD47 Signaling-Mediated Neutrophil Extracellular Traps Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Identification and analysis of neutrophil extracellular trap-related genes in periodontitis via bioinformatics and experimental verification.BMC oral health · 2025Article
- A Hypoxia-Inflammation Cycle and Multiple Sclerosis: Mechanisms and Therapeutic Implications.Current treatment options in neurology · 2025Review
- Pyroptosis for osteoarthritis treatment: insights into cellular and molecular interactions inflammatory.Frontiers in immunology · 2025Review
- Nanoparticle-based itaconate treatment recapitulates low-cholesterol/low-fat diet-induced atherosclerotic plaque resolution.Cell reports · 2024Article
- Intracellular checkpoints for NK cell cancer immunotherapy.Frontiers of medicine · 2024Review
- The role and therapeutic potential of itaconate in lung disease.Cellular & molecular biology letters · 2024Review
- Neutrophil extracellular traps in homeostasis and disease.Signal transduction and targeted therapy · 2024Review
- The Aconitate Decarboxylase 1/Itaconate Pathway Modulates Immune Dysregulation and Associates with Cardiovascular Disease Markers and Disease Activity in Systemic Lupus Erythematosus.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- The aconitate decarboxylase 1/itaconate pathway modulates immune dysregulation and associates with cardiovascular disease markers in SLE.medRxiv : the preprint server for health sciences · 2024Article
- Control of immune cell signaling by the immuno-metabolite itaconate.Frontiers in immunology · 2024Review
- Itaconate to treat acute lung injury: recent advances and insights from preclinical models.American journal of translational research · 2024Review
- The Application of Drugs and Nano-Therapies Targeting Immune Cells in Hypoxic Inflammation.International journal of nanomedicine · 2024Review
- Neutrophil (dys)function due to altered immuno-metabolic axis in type 2 diabetes: implications in combating infections.Human cell · 2023Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neutrophil extracellular traps (NETs) immobilize pathogens during early stages of systemic inflammation but as the reaction progresses they become detrimental to endothelial cells and the organ-specific cells. For this reason it would be of importance to control their formation by either physiological or pharmacological means. Endogenously, formation of NETs is under control of cellular and whole organism metabolism as shown previously in the course of bacterial systemic inflammation, obesity or the combination of the two. Numerous leukocytes are subjected to immunometabolic regulation and in macrophages exposure to lipopolysaccharide (LPS) leads to two breaks in the Krebs cycle that impact this cell functioning. As a consequence of the first break, anti-microbial itaconic acid (itaconate) is produced whereas the second break activates hypoxia-inducible factor-1α (Hif-1α). In turn, itaconate activates transcription of the anti-inflammatory nuclear factor erythroid 2-related factor 2 (Nrf2) which upregulates cyto-protective heme oxygenase (HO-1). Here we report that exogenously added derivative of the itaconic acid, 4-octyl itaconate (4-OI), diminishes formation of NETs by neutrophils of either normal (lean) or obese mice, and independently of the age of the animals or immunoaging. Elucidating the mechanism of this inhibition we unravel that although Nrf2/HO-1 expression itself is not altered by 4-OI, it is up-regulated when compared against the NET formation while Hif-1α is downregulated in 4-OI-pre-treated LPS-stimulated neutrophils in either way. We further show that blockage of Hif-1α by its specific inhibitor diminishes NET release as does inhibition by 4-OI. Also inhibition of HO-1 activity correlates with diminished LPS-induced NET release upon pre-treatment with 4-OI albeit LPS alone induced NETs are not HO-1-dependent. In summary, we unravel that 4-OI inhibits NET formation by murine neutrophils independently of their origin (health vs. metabolically challenged animals) and the age of individuals/immunosenescence
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