ArticleJournal of neuroinflammation2021
Microglia and macrophage exhibit attenuated inflammatory response and ferroptosis resistance after RSL3 stimulation via increasing Nrf2 expression.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
124 citing papers in PubMed, 1 synthesis or guideline pooled it, 194 citations in OpenAlex.
- Macrophage Subsets and Death Are Responsible for Atherosclerotic Plaque Formation.Frontiers in immunology · 2022Pooled it
- HAND in Africa: prevalence, diagnostic challenges and the search for objective markers.Journal of neurovirology · 2026Review
- Comorbid mechanisms of neuroinflammation and astrocytic ferroptosis in neurological disorders: A vicious cycle (Review).Biomedical reports · 2026Review
- SIRT1 Activation Ameliorates Neuroinflammation and Cognitive Impairment in a Murine SAE Model and is Associated with the Nrf2/GPX4 Pathway.Neurochemical research · 2026Article
- ACSL4-mediated astrocyte ferroptosis augments neuroinflammation and exacerbates NMOSD pathology.Cell death and differentiation · 2026Article
- Exploring the Molecular Mechanisms of SB216763 in the Therapeutic Intervention of Pulmonary Fibrosis Based on Macrophage Functional Plasticity.Fundamental & clinical pharmacology · 2026Article
- N 6 -methyladenosine modification regulates cell death in cognitive impairment.Neural regeneration research · 2026Article
- Forsythoside A alleviates experimental autoimmune encephalomyelitis by targeting Tnfaip2.Chinese medicine · 2026Article
- DLL1-mediated ferroptosis resistance via the Notch-Nrf2/GPX4 axis drives cisplatin resistance in ovarian cancer.Cancer & metabolism · 2026Article
- Sympathetic signaling activation alleviated acute respiratory distress syndrome via the HDC/SLC7A11 axis in lipopolysaccharide-induced macrophages.Cell death discovery · 2026Article
- Fenofibrate mitigates microglial activation by reprogramming lipid metabolism and inhibiting ferroptosis.Molecular and cellular biochemistry · 2026Article
- Ferroptosis-driven metabolic reprogramming in macrophages: Reshaping glucose utilization landscapes.Chinese medical journal · 2026Review
- Hierarchically collapsible nanoactuator modulates mitochondrial ferroptosis-bioenergetic homeostasis cascade to decouple ischemic stroke.Cell reports. Medicine · 2026Article
- Non-apoptotic Regulated Cell Death Mechanisms in Sepsis and their Therapeutic Potential.Inflammation · 2026Review
- Pharmacological intervention of Chinese medicine via regulating ferroptosis in gastric cancer.Chinese medicine · 2026Review
- Ferroptosis associated with secondary brain damage induced by hypertensive underlying biological processes in intracerebral hemorrhage and therapeutic prospects.European journal of medical research · 2026Review
- Hyperbaric oxygen preconditioning alleviates spinal cord injury by inhibiting pro-inflammatory astrocyte polarization in a rat model of decompression sickness.Frontiers in immunology · 2026Article
- Ferroptosis in microglial activation: a systematic review and multidata comparison.Brain communications · 2026Review
- Ferroptosis in retinal neurodegeneration: mechanistic vulnerability, therapeutic targeting, and translational barriers.Frontiers in medicine · 2026Review
- Ferroptosis-immune crosstalk in CNS diseases: mechanisms and translational insights.Frontiers in immunology · 2026Review
64 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMany neurological diseases involve neuroinflammation, during which overproduction of cytokines by immune cells, especially microglia, can aggregate neuronal death. Ferroptosis is a recently discovered cell metabolism-related form of cell death and RSL3 is a well-known inducer of cell ferroptosis. Here, we aimed to investigate the effects of RSL3 in neuroinflammation and sensitivity of different type of microglia and macrophage to ferroptosis.
methodsHere, we used quantitative RT-PCR analysis and ELISA analysis to analyze the production of proinflammatory cytokine production of microglia and macrophages after lipopolysaccharides (LPS) stimulation. We used CCK8, LDH, and flow cytometry analysis to evaluate the sensitivity of different microglia and macrophages to RSL3-induced ferroptosis. Western blot was used to test the activation of inflammatory signaling pathway and knockdown efficiency. SiRNA-mediated interference was conducted to knockdown GPX4 or Nrf2 in BV2 microglia. Intraperitoneal injection of LPS was performed to evaluate systemic inflammation and neuroinflammation severity in in vivo conditions.
resultsWe found that ferroptosis inducer RSL3 inhibited lipopolysaccharides (LPS)-induced inflammation of microglia and peritoneal macrophages (PMs) in a cell ferroptosis-independent manner, whereas cell ferroptosis-conditioned medium significantly triggered inflammation of microglia and PMs. Different type of microglia and macrophages showed varied sensitivity to RSL3-induced ferroptosis. Mechanistically, RSL3 induced Nrf2 protein expression to inhibit RNA Polymerase II recruitment to transcription start site of proinflammatory cytokine genes to repress cytokine transcription, and protect cells from ferroptosis. Furthermore, simultaneously injection of RSL3 and Fer-1 ameliorated LPS-induced neuroinflammation in in vivo conditions.
conclusionsThese data revealed the proinflammatory role of ferroptosis in microglia and macrophages, identified RSL3 as a novel inhibitor of LPS-induced inflammation, and uncovered the molecular regulation of microglia and macrophage sensitivity to ferroptosis. Thus, targeting ferroptosis in diseases by using RSL3 should consider both the pro-ferroptosis effect and the anti-inflammation effect to achieve optimal outcome.
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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 Socratic graph.