ArticleThe Journal of biological chemistry2015
Caspase-8 as an Effector and Regulator of NLRP3 Inflammasome Signaling.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 2 of them syntheses that pooled it.
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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
147 citing papers in PubMed, 2 syntheses or guidelines pooled it, 219 citations in OpenAlex.
- The impact of post-translational modifications and subcellular localization on NLRP3 inflammasome activation: A systematic review.Cell communication and signaling : CCS · 2025Pooled it
- Role of Inflammasomes in Neuroimmune and Neurodegenerative Diseases: A Systematic Review.Mediators of inflammation · 2018Pooled it
- IL1 Receptor Antagonist Controls Transcriptional Signature of Inflammation in Patients with Metastatic Breast Cancer.Cancer research · 2018Trial
- P2X4 Receptor Antagonists Exert Anti-Inflammatory Effects via NLRP3 Inflammasome in a Murine Model of Colitis.ACS pharmacology & translational science · 2026Article
- The NLRP3 inflammasome at the crossroads of innate immune signaling and cell death.Cellular & molecular immunology · 2026Review
- Article
- Interleukin-18 armours antitumour immune effectors.Nature reviews. Immunology · 2026Review
- An "old" cytokine's new trick: IL-1β in B cells and the germinal center.Function (Oxford, England) · 2026Review
- Interconnected cell death pathways: central mechanisms and therapeutic targets in impaired follicular development of polycystic ovary syndrome.Journal of ovarian research · 2026Review
- Inflammasome adaptor ASC promotes sustained neuroinflammation and mild cognitive impairment in a closed-head injury model.The Journal of clinical investigation · 2026Article
- Caspase-1 in cancer and inflammatory diseases: a potential therapeutic target.Apoptosis : an international journal on programmed cell death · 2026Review
- Pro-inflammatory response of human iPSC-derived intestinal epithelial monolayers towards microbial toxins LPS and nigericin.Archives of toxicology · 2026Article
- Tuoli Tounong decoction promotes lesion resolution in granulomatous lobular mastitis by remodeling a Caspase-8-associated PANoptosis-like cell death network.Frontiers in immunology · 2026Article
- The role of NLRP3 inflammasome in age-related macular degeneration: mechanisms and therapeutic prospects.Frontiers in aging neuroscience · 2026Review
- 3'-hydroxypuerarin mitigates LPS-induced acute lung injury by inhibiting TLR4 activation-mediated NF-κB p65/NLRP3/GSDMD signaling.Frontiers in immunology · 2026Article
- Regulated cell death in sepsis-associated liver injury: molecular mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- NLRP3 inflammasome in cardiovascular diseases: molecular mechanisms and advances in targeted drug research.Frontiers in immunology · 2026Review
- Inhibition of the inflammasome ameliorates orthologous polycystic kidney disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- 7-Methoxyflavanone Alleviates LPS-Induced Acute Lung Injury by Suppressing TLR4/NF-κB p65 and ROS/Txnip/NLRP3 Signaling.Biology · 2025Article
- Matrix-M adjuvant triggers inflammasome activation and enables antigen cross-presentation through induction of lysosomal membrane permeabilization.NPJ vaccines · 2025Article
87 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
We recently described the induction of noncanonical IL-1β processing via caspase-8 recruited to ripoptosome signaling platforms in myeloid leukocytes. Here, we demonstrate that activated NLRP3·ASC inflammasomes recruit caspase-8 to drive IL-1β processing in murine bone marrow-derived dendritic cells (BMDC) independent of caspase-1 and -11. Sustained stimulation (>2 h) of LPS-primed caspase-1-deficient (Casp1/11(-/-)) BMDC with the canonical NLRP3 inflammasome agonist nigericin results in release of bioactive IL-1β in conjunction with robust caspase-8 activation. This IL-1β processing and caspase-8 activation do not proceed in Nlrp3(-/-) or Asc(-/-) BMDC and are suppressed by pharmacological inhibition of caspase-8, indicating that caspase-8 can act as a direct IL-1β-converting enzyme during NLRP3 inflammasome activation. In contrast to the rapid caspase-1-mediated death of wild type (WT) BMDC via NLRP3-dependent pyroptosis, nigericin-stimulated Casp1/11(-/-) BMDC exhibit markedly delayed cell death via NLRP3-dependent apoptosis. Biochemical analyses of WT and Casp1/11(-/-) BMDC indicated that caspase-8 is proteolytically processed within detergent-insoluble ASC-enriched protein complexes prior to extracellular export during nigericin treatment. Although nigericin-stimulated caspase-1 activation and activity are only modestly attenuated in caspase-8-deficient (Casp8(-/-)Rip3(-/-)) BMDC, these cells do not exhibit the rapid loss of viability of WT cells. These results support a contribution of caspase-8 to both IL-1β production and regulated death signaling via NLRP3 inflammasomes. In the absence of caspase-1, NLRP3 inflammasomes directly utilize caspase-8 as both a pro-apoptotic initiator and major IL-1β-converting protease. In the presence of caspase-1, caspase-8 acts as a positive modulator of the NLRP3-dependent caspase-1 signaling cascades that drive both IL-1β production and pyroptotic death.
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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.