ArticleImmunology and cell biology2020
Dimethyl itaconate protects against fungal keratitis by activating the Nrf2/HO-1 signaling pathway.
Article in Immunology and cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 77 citations in OpenAlex.
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Dimethyl itaconate attenuates dextran sulfate sodium-induced ulcerative colitis in BALB/c mice: investigations on the TXNIP/NLRP3 inflammasome signaling pathway.Inflammopharmacology · 2026Article
- Itaconate-based nanoparticles induce immunometabolic reprogramming in macrophages and alleviate diet-induced obesity.Research square · 2026Article
- Metabolic control of neuroinflammation: focus on itaconate and its derivatives in CNS disorders.Frontiers in immunology · 2026Review
- Neuroprotectin D1 regulating the inflammation and nerve restoration inInternational journal of ophthalmology · 2026Article
- Dimethyl Itaconate Alleviates Escherichia coli-Induced Endometritis Through the Guanosine-CXCL14 Axis via Increasing the Abundance of norank_f_Muribaculaceae.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Desensitization of TRPA1 by dimethyl itaconate attenuates acute and chronic pain in mice.Frontiers in pharmacology · 2025Article
- Rutin-Activated Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Attenuates Corneal and Heart Damage in Mice.Pharmaceuticals (Basel, Switzerland) · 2024Article
- The role and therapeutic potential of itaconate in lung disease.Cellular & molecular biology letters · 2024Review
- Dimethyl itaconate is effective in host-directed antimicrobial responses against mycobacterial infections through multifaceted innate immune pathways.Cell & bioscience · 2023Article
- Dimethyl itaconate ameliorates cognitive impairment induced by a high-fat diet via the gut-brain axis in mice.Microbiome · 2023Article
- Protective effects of dietary dimethyl itaconate supplementation on oxidative stress, inflammation, and apoptosis in broilers under chronic heat stress.Journal of animal science · 2023Article
- Modern Technologies in Diagnosis of Fungal Keratitis (Review).Sovremennye tekhnologii v meditsine · 2023Review
- Itaconate family-based host-directed therapeutics for infections.Frontiers in immunology · 2023Review
- Gallic Acid Ameliorates Aspergillus Fumigatus Keratitis Through Reducing Fungal Load and Suppressing the Inflammatory Response.Investigative ophthalmology & visual science · 2022Article
- Aconitate decarboxylase 1 regulates glucose homeostasis and obesity in mice.Obesity (Silver Spring, Md.) · 2022Article
- A metabolite attenuates neuroinflammation, synaptic loss and cognitive deficits induced by chronic infection ofFrontiers in immunology · 2022Article
- Preparation of a Nanobody Specific to Dectin 1 and Its Anti-inflammatory Effects on Fungal Keratitis.International journal of nanomedicine · 2022Article
- Itaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection.PLoS pathogens · 2022Article
- Dimethyl itaconate alleviates the pyroptosis of macrophages through oxidative stress.BMC immunology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dimethyl itaconate (DI) is a membrane-permeable itaconate derivative with anti-inflammatory functions. However, the anti-inflammatory effect of DI has never been studied in fungal keratitis. In this study, we tested the protective effect of DI against fungal keratitis and assessed the role of NF-E2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1) signaling in this process. Eyes of C57BL/6 (B6) mice were treated with 2 mm DI after infection with Aspergillus fumigatus. Human corneal epithelial cells (HCECs) were pretreated with 0.25 mm DI and then incubated with A. fumigatus. Clinical scoring, slit-lamp photography, myeloperoxidase determination, flow cytometry and immunostaining were used to assess the disease response and treatment efficacy. PCR, Western blot and ELISA were used to assess the expression of interleukin-1β (IL-1β), chemokine (C-X-C motif) ligand 1, IL-6, IL-8, Nrf2 and HO-1. In addition, quantification of viable fungi, absorbance assays and fluorimetry were used to measure DI fungistatic activity. We observed that DI-treated eyes showed decreased clinical scores, fungal loads, polymorphonuclear neutrophil (PMN) infiltration and cytokine expression, compared with phosphate-buffered saline-treated infected eyes. DI treatment decreased the cytokine levels in infected corneas and in HCECs stimulated with A. fumigatus. Moreover, DI treatment increased Nrf2 and HO-1 expression in corneas and nuclear Nrf2 accumulation in HCECs. DI-induced cytokine downregulation was inhibited by pretreatment with an Nrf2 or HO-1 inhibitor. Finally, DI treatment reduced the A. fumigatus absorbance and fungal mass. These data indicate that DI protects against fungal keratitis by limiting inflammation via the Nrf2/HO-1 signaling pathway and that DI inhibits the growth of A. fumigatus.
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