ArticleJournal of immunology (Baltimore, Md. : 1950)2021
Noncanonical Roles of Caspase-4 and Caspase-5 in Heme-Driven IL-1β Release and Cell Death.
Article in Journal of immunology (Baltimore, Md. : 1950), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 36 citations in OpenAlex.
- An overview of human inflammasomes: Activation and regulation.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Heme and hemozoin induce platelet cell death through UPR-induced apoptosis and ferroptosis in vivax malaria.Blood advances · 2026Article
- Non-apoptotic Regulated Cell Death Mechanisms in Sepsis and their Therapeutic Potential.Inflammation · 2026Review
- Gut microbiota in genetic diseases: from Mendelian disorders to complex traits.Frontiers in immunology · 2026Review
- The mechanisms by which free heme exacerbates sepsis and the potential therapeutic targets.Frontiers in immunology · 2026Review
- One trigger, two fates: hemolysate shapes neutrophil extracellular traps (NETs) formation in a context-dependent manner.Frontiers in immunology · 2026Article
- Heme Modulates Bladder Contractility Through the HO-CO-sGC-cGMP Pathway: Insights into Sickle Cell Disease-Associated Bladder Dysfunction.Antioxidants (Basel, Switzerland) · 2025Article
- Targeting inflammasomes as an immunotherapeutic strategy for cancer.Journal of translational medicine · 2025Review
- Mitochondrial Dysfunction is a Crucial Immune Checkpoint for Neuroinflammation and Neurodegeneration: mtDAMPs in Focus.Molecular neurobiology · 2025Review
- Interplay between PI3k/AKT signaling and caspase pathway in Alzheimer disease: mechanism and therapeutic implications.Inflammopharmacology · 2025Review
- Exacerbated Activation of the NLRP3 Inflammasome in the Placentas from Women Who Developed Chronic Venous Disease during Pregnancy.International journal of molecular sciences · 2024Article
- Caspase-5: Structure, Pro-Inflammatory Activity and Evolution.Biomolecules · 2024Review
- The global role of G6PD in infection and immunity.Frontiers in immunology · 2024Review
- The clinical relevance of heme detoxification by the macrophage heme oxygenase system.Frontiers in immunology · 2024Review
- Article
- Placentas from Women with Late-Onset Preeclampsia Exhibit Increased Expression of the NLRP3 Inflammasome Machinery.Biomolecules · 2023Article
- Histidine-rich protein II nanoparticle delivery of heme iron load drives endothelial inflammation in cerebral malaria.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Mitochondrial control of inflammation.Nature reviews. Immunology · 2023Review
- The NLRP3 inflammasome fires up heme-induced inflammation in hemolytic conditions.Translational research : the journal of laboratory and clinical medicine · 2023Review
- Pyroptosis-Related Signature Predicts the Progression of Ulcerative Colitis and Colitis-Associated Colorectal Cancer as well as the Anti-TNF Therapeutic Response.Journal of immunology research · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Excessive release of heme from RBCs is a key pathophysiological feature of several disease states, including bacterial sepsis, malaria, and sickle cell disease. This hemolysis results in an increased level of free heme that has been implicated in the inflammatory activation of monocytes, macrophages, and the endothelium. In this study, we show that extracellular heme engages the human inflammatory caspases, caspase-1, caspase-4, and caspase-5, resulting in the release of IL-1β. Heme-induced IL-1β release was further increased in macrophages from patients with sickle cell disease. In human primary macrophages, heme activated caspase-1 in an inflammasome-dependent manner, but heme-induced activation of caspase-4 and caspase-5 was independent of canonical inflammasomes. Furthermore, we show that both caspase-4 and caspase-5 are essential for heme-induced IL-1β release, whereas caspase-4 is the primary contributor to heme-induced cell death. Together, we have identified that extracellular heme is a damage-associated molecular pattern that can engage canonical and noncanonical inflammasome activation as a key mediator of inflammation in macrophages.
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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.