Pyroptosis
Pyroptosis is a form of regulated cell death characterized by inflammatory signaling, disruption of the plasma membrane, and release of intracellular danger signals.
Pyroptosis is a form of regulated cell death characterized by inflammatory signaling, disruption of the plasma membrane, and release of intracellular danger signals. It is commonly initiated by inflammasomes such as the NLRP3 inflammasome, which activate caspase-1. Caspase-1 cleaves Gasdermin D (GSDMD), releasing its pore-forming fragment and promoting cellular swelling, membrane rupture, and secretion of interleukin-1β (IL-1β) and interleukin-18 (IL-18). Pyroptosis can also be initiated through non-canonical inflammasome pathways, which respond to cytosolic lipopolysaccharide and activate inflammatory caspases that converge on GSDMD.
Additional pyroptotic routes involve apoptotic caspases and other gasdermins. For example, caspase-3 can cleave Gasdermin E (GSDME), thereby redirecting apoptotic signaling toward a pyroptosis-like, inflammatory form of cell death. Release of high mobility group box 1 (HMGB1), proinflammatory cytokines, and other damage-associated molecular patterns can amplify inflammation and influence macrophage activity, antigen presentation, and adaptive immune responses. In contrast with the generally immunologically quiet dismantling associated with apoptosis, pyroptosis is considered an immunogenic cell-death modality that can stimulate dendritic-cell and T-cell responses; it is therefore studied both as a driver of inflammatory disease and as a potential mechanism for cancer therapy.
Rebuilt from PubMed 18 Sept 2026 · no new papers today
Where the papers sit
14 papers study pyroptosis directly. The themes below are drawn from those 14. 1 paradigm shift follows.
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Cancer Immunogenic Cell Death : Nanoplatforms and photosensitizers are using GSDME-linked pyroptosis to turn tumor death into immune stimulation. Recurring endpoints include dendritic-cell activation, T-cell responses, tumor-antigen release and improved radiotherapy. 6 papers · 42.9%
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Inflammation and Fibrosis : NLRP3, caspase-1, GSDMD and IL-1β recur as targets for limiting pyroptosis in sepsis, organ injury, aging and fibrotic disease. Small molecules, natural compounds and biomaterials are being tested to reduce inflammatory damage and restore tissue function. 6 papers · 42.9%
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Epigenetic Regulation of Cell Death : m6A and lncRNA regulation, including the METTL14–MEG8–WNT7A axis, is being linked to inflammasome-mediated cell death. The work is moving toward molecular suppression of pyroptosis to protect placental trophoblasts and injured peripheral nerves. 2 papers · 14.3%
Pyroptosis can be therapeutically routed through apoptotic caspases and GSDME rather than being confined to inflammasome–caspase-1–GSDMD signaling
Mito-Ir photodynamic therapy in breast cancer and QSSC@Exo-LNP nanotherapy in glioblastoma independently found that mitochondrial or death-receptor-linked apoptotic caspases can activate GSDME-mediated pyroptosis: light-activated Mito-Ir used the caspase-3/GSDME pathway, while chlorogenic acid in QSSC@Exo-LNP initiated GSDME pyroptosis through caspase-8 and amplified it through caspase-3 42489638Jul 42466899Jul. Much of the set instead treats pyroptosis through inflammasome-associated caspase-1 and GSDMD, particularly in inflammatory and tissue-injury models. The change is that pyroptosis is not restricted to the canonical inflammatory machinery; apoptotic signaling can be deliberately rerouted into an immunogenic, GSDME-dependent death program, expanding therapeutic design beyond direct inflammasome activation 42489638Jul 42466899Jul.
Recent Findings on pyroptosis
Cancer Immunotherapy and GSDME: GSDME delivery and activation are being used to convert tumor-cell pyroptosis into antitumor immunity. Biomimetic nanovesicles, exosome-liposome hybrids, photosensitizers, and single-atom nanozymes increased pyroptosis, released tumor antigens and cytokines, and promoted dendritic cell maturation, macrophage reprogramming, or T-cell activation 42492635Jul42466899Jul42489638Jul42424164Jul. Radiotherapy partnered with GSDME delivery, while mitochondrial dysfunction and reactive oxygen species activated the CASP3/GSDME pathway in breast cancer 42492635Jul42489638Jul. Glioblastoma models used EGFR inhibition and caspase-8 activation to amplify GSDME-mediated pyroptosis across the blood-brain barrier, whereas prostate cancer models combined pyroptosis with disulfidptosis and metabolic reprogramming 42466899Jul42424164Jul. Lung-cancer research places pyroptosis alongside ferroptosis and necroptosis as immunogenic cell-death pathways that can convert immune-resistant tumors into immune-sensitive states 41998294Apr.
Canonical Inflammasome Signaling: Caspase-1–GSDMD signaling links pyroptosis to both immunogenic tumor control and inflammatory tissue injury. Anwulignan activated caspase-1-dependent GSDMD pyroptosis, enhanced proteasome-inhibitor activity against multiple myeloma, and increased T-cell proportions, while cartilage repair, diabetic liver injury, granulomatous lobular mastitis, and sepsis studies instead improved outcomes by suppressing inflammasome-associated pyroptosis 42704369Sep42576623Aug42219549May42142128May. Curcumin, TNF-α inhibition, oxyphenbutazone, and Tuolitounong decoction reduced NLRP3, caspase-1, GSDMD, or upstream HMGB1/TLR4/MyD88/NF-κB signaling in their respective injury models 42576623Aug42219549May42150290May42142128May. Oxyphenbutazone also inhibited non-canonical inflammasome activation near caspase-11, while anwulignan deliberately preserved canonical pyroptosis to overcome drug resistance and stimulate immunity 42150290May42704369Sep. This work is therefore moving toward context-specific control of inflammasome signaling, with selective inhibition for tissue protection and deliberate activation for immunogenic cell death.
METTL14 and aconitine reduced inflammasome-linked pyroptosis while targeting distinct tissue-injury mechanisms. In gestational diabetes, METTL14 overexpression used YTHDF2-mediated m6A modification to suppress lncRNA MEG8, reduce EZH2 recruitment and H3K27me3 at the WNT7A promoter, and alleviate trophoblast pyroptosis 42726311Sep. In peripheral-nerve injury, aconitine inhibited NLRP3 inflammasome-mediated pyroptosis, reduced M1 macrophage polarization and proinflammatory cytokine secretion, and promoted regeneration through TLR4/MyD88/NF-κB and STING/IRF3 blockade 42480279Jul. These findings direct future work toward upstream epitranscriptomic, inflammatory, and macrophage-regulatory targets for tissue-specific pyroptosis control.
Written from 14 PubMed abstracts, each one cited by PMID above. Published: 2026-08-28. Last written: 2026-09-13 by GPT. Drafted by language models from published abstracts; not medical advice.