ArticleProceedings of the National Academy of Sciences of the United States of America2004
Phospholipases C and A2 control lysosome-mediated IL-1 beta secretion: Implications for inflammatory processes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers.
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Who cites it
156 citing papers in PubMed, 401 citations in OpenAlex.
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- The role of maternal infections in neurodevelopmental psychiatric disorders: focus on the P2X7/NLRP3/IL-1β signalling pathway.Journal of neuroinflammation · 2025Review
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- Molecular mechanisms and pathological implications of unconventional protein secretion in human disease: from cellular stress to therapeutic targeting.Molecular biology reports · 2025Review
- NLRP3 inflammasome in cardiovascular diseases: an update.Frontiers in immunology · 2025Review
- Microglial P2YNeuron · 2024Article
- Identification of a short sequence motif in the influenza A virus pathogenicity factor PB1-F2 required for inhibition of human NLRP3.Journal of virology · 2024Article
- Methods to Study NLR in Human Blood Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Macrophage IL-1β-positive microvesicles exhibit thrombo-inflammatory properties and are detectable in patients with active juvenile idiopathic arthritis.Frontiers in immunology · 2023Article
- Lysosomal cathepsins act in concert with Gasdermin-D during NAIP/NLRC4-dependent IL-1β secretion.Cell death & disease · 2022Article
- Analysis of Gene Single Nucleotide Polymorphisms in COVID-19 Disease Highlighting the Susceptibility and the Severity towards the Infection.Diagnostics (Basel, Switzerland) · 2022Article
- Pan HDACi Valproic Acid and Trichostatin A Show Apparently Contrasting Inflammatory Responses in Cultured J774A.1 Macrophages.Epigenomes · 2022Article
- GM-CSF suppresses antioxidant signaling and drives IL-1β secretion through NRF2 downregulation.EMBO reports · 2022Article
- Intracellular flow cytometry staining of antibody-secreting cells using phycoerythrin-conjugated antibodies: pitfalls and solutions.Antibody therapeutics · 2022Article
- Cytokines and Inflammation in Meniere Disease.Clinical and experimental otorhinolaryngology · 2022Review
- Intervertebral disc cell chondroptosis elicits neutrophil response inFrontiers in immunology · 2022Article
- Erythropoietin Enhances Post-ischemic Migration and Phagocytosis and Alleviates the Activation of Inflammasomes in Human Microglial Cells.Frontiers in cellular neuroscience · 2022Article
- P2X4 Receptors Mediate CaInternational journal of molecular sciences · 2021Article
96 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Blocking the activity of IL-1 beta has entered the clinical arena of treating autoimmune diseases. However, a successful outcome of this approach requires a clear definition of the mechanisms controlling IL-1 beta release. These are still unclear as IL-1 beta, lacking a secretory signal peptide, follows a nonclassical pathway of secretion. Here, we analyze the molecular mechanism(s) undergoing IL-1 beta processing and release in human monocytes and provide a unifying model for the regulated secretion of the cytokine. Our data show that in a first step, pro-caspase-1 and endotoxin-induced pro-IL-1 beta are targeted in part to specialized secretory lysosomes, where they colocalize with other lysosomal proteins. Externalization of mature IL-1 beta and caspase-1 together with lysosomal proteins is then facilitated by extracellular ATP. ATP triggers the efflux of K(+) from the cell, followed by Ca(2+) influx and activation of three phospholipases: phosphatidylcholine-specific phospholipase C and calcium-independent and -dependent phospholipase A(2). Whereas calcium-independent phospholipase A(2) is involved in processing, phosphatidylcholine-specific phospholipase C and calcium-dependent phospholipase A(2) are required for secretion. Dissection of the events that follow ATP triggering allowed to demonstrate that K(+) efflux is responsible for phosphatidylcholine-specific phospholipase C induction, which in turn allows the rise in intracellular free calcium concentration required for activation of phospholipase A(2). This activation is ultimately responsible for lysosome exocytosis and IL-1 beta secretion.
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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 OpenQuestion graph.