ArticleCell death discovery2022
Itaconate inhibits ferroptosis of macrophage via Nrf2 pathways against sepsis-induced acute lung injury.
Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers.
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Who cites it
149 citing papers in PubMed, 282 citations in OpenAlex.
- Itaconate metabolism in regulated cell death.Molecular and cellular biochemistry · 2026Review
- RUNX3: a regulator of macrophage apoptosis with positive prognostic impact in sepsis.Genes & genomics · 2026Article
- Microparticles synthesized from itaconate polyesters enable metabolite delivery and elicit immunoregulatory outcomes.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- 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
- Four-Octyl Itaconate Alleviates Enterococcus faecalis-Induced Apical Periodontitis by Inhibiting Macrophage M1 Polarisation.International endodontic journal · 2026Article
- Ferroptosis-related TFRC: a potential therapeutic target in sepsis and regulatory effect of γ-Tocotrienol.Human genomics · 2026Article
- Nrf2 signaling pathway and its molecular regulatory mechanism.Journal of Zhejiang University. Science. B · 2026Review
- Article
- Sympathetic signaling activation alleviated acute respiratory distress syndrome via the HDC/SLC7A11 axis in lipopolysaccharide-induced macrophages.Cell death discovery · 2026Article
- Targeted silencing of CLYBL with platelet-mimetic siRNA nanoparticles drives itaconate-mediated macrophage reprogramming and protects against sepsis-triggered lung cell death.Cell death discovery · 2026Article
- OGDH primes macrophage for M1-like polarization and ferroptosis in sepsis associated acute lung injury.Respiratory research · 2026Article
- Ferroptosis-driven metabolic reprogramming in macrophages: Reshaping glucose utilization landscapes.Chinese medical journal · 2026Review
- ACOD1-itaconate in macrophage attenuates oxidative stress and inflammation in benign airway stenosis by upregulating and transferring FTH1.Redox biology · 2026Article
- NIR-responsive prussian Blue/Fer-1 co-loaded nanozymes for synergistic therapy of acute lung injury.Journal of nanobiotechnology · 2026Article
- An immune-mediated effect of the antibiotic cefiderocol on LPS-induced acute lung injury.Antimicrobial agents and chemotherapy · 2026Article
- Cumambrin B Alleviates Sepsis-Associated Acute Lung Injury by Activating the Nrf2/HO-1 Pathway.Biomedicines · 2026Article
- Protective role of IRG1/itaconate in acute myocardial injury: association with NLRP3 inflammasome and oxidative stress.Scientific reports · 2026Article
- Mast Cell-Derived CXCL4: A Key Mediator of Ferroptosis and Cardiac Damage in Septic Cardiomyopathy.Immunity, inflammation and disease · 2026Article
- Microplastic-Induced Macrophage Dysfunction Drives Lung Tumor Progression through Glutathione Imbalance.ACS nano · 2026Article
89 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Itaconate, a metabolite produced during inflammatory macrophage activation, has been extensively described to be involved in immunoregulation, oxidative stress, and lipid peroxidation. As a form of iron and lipid hydroperoxide-dependent regulated cell death, ferroptosis plays a critical role in sepsis-induced acute lung injury (ALI). However, the relationship between itaconate and ferroptosis remains unclear. This study aims to explore the regulatory role of itaconate on ferroptosis in sepsis-induced ALI. In in vivo experiments, mice were injected with LPS (10 mg/kg) for 12 h to generate experimental sepsis models. Differential gene expression analysis indicated that genes associated with ferroptosis existed significant differences after itaconate pretreatment. 4-octyl itaconate (4-OI), a cell-permeable derivative of endogenous itaconate, can significantly alleviate lung injury, increase LPS-induced levels of glutathione peroxidase 4 (GPX4) and reduce prostaglandin-endoperoxide synthase 2 (PTGS2), malonaldehyde (MDA), and lipid ROS. In vitro experiments showed that both 4-OI and ferrostatin-1 inhibited LPS-induced lipid peroxidation and injury of THP-1 macrophage. Mechanistically, we identified that 4-OI inhibited the GPX4-dependent lipid peroxidation through increased accumulation and activation of Nrf2. The silence of Nrf2 abolished the inhibition of ferroptosis from 4-OI in THP-1 cells. Additionally, the protection of 4-OI for ALI was abolished in Nrf2-knockout mice. We concluded that ferroptosis was one of the critical mechanisms contributing to sepsis-induced ALI. Itaconate is promising as a therapeutic candidate against ALI through inhibiting ferroptosis.
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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.