ArticleCell proliferation2024
4-Octyl itaconate blocks GSDMB-mediated pyroptosis and restricts inflammation by inactivating granzyme A.
Article in Cell proliferation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Hypoxia-pyroptosis-associated long noncoding RNAs as prognostic biomarkers in lung cancer: a systematic review and meta-analysis.Respiratory research & clinical practice · 2026Pooled it
- 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
- Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026Review
- Epithelial-immune interface in asthma: Mechanistic insights driving novel therapeutic strategies.Seminars in immunopathology · 2026Review
- Targeting pyroptosis to treat aortic aneurysms: From mechanism to drug discovery (Review).International journal of molecular medicine · 2026Review
- Decoding the molecular mechanisms of pyroptosis and its therapeutic development prospects.Frontiers in cell and developmental biology · 2026Review
- Macrophage pyroptosis in inflammatory bowel disease: mechanistic insights, pathological roles and treatment strategies.Frontiers in immunology · 2026Review
- Article
- Integrated bioinformatics analysis of biomarkers and pathways to explore the mechanisms and molecular targets related to allergic rhinitis and pyroptosis.Scientific reports · 2025Article
- 4-Octyl itaconate blocks GSDMB-mediated pyroptosis and restricts inflammation by inactivating granzyme A.Cell proliferation · 2024Article
- Crosstalk of pyroptosis and cytokine in the tumor microenvironment: from mechanisms to clinical implication.Molecular cancer · 2024Review
- Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
GSDMB-mediated pyroptosis facilitates a pro-inflammatory immune microenvironment and needs to be tightly regulated to avoid excessive inflammation. Here, we provide evidence that itaconate and its cell-permeable derivative 4-octyl itaconate (4-OI) can significantly inhibit GSDMB-rendered pyroptotic activity independent of Nrf2. 4-OI interferes proteolytic process of GSDMB by directly modifying Cys54, Cys148 and Ser212 on granzyme A (GrzA), a serine protease that site-specifically cleaves the inter-domain linker of GSDMB, instead of interaction with GSDMB, thereby blocking pyroptosis and exerts anti-inflammatory effects. Moreover, 4-OI alleviates inflammation by suppressing GSDMB-induced pyroptotic cell death during acute colitis models in intestinal epithelial GSDMB conditional transgenic mice. Our data expand the role of 4-OI as a crucial immunometabolic derivative that regulates innate immunity and inflammation through a newly identified posttranslational modification, and targeting of pyroptosis by 4-OI therefore holds potent therapeutic potential for primarily inflammatory and/or autoimmune diseases.
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Registered trials
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