{"id":"3441e006-b6b4-561c-a22c-5489ba0c7513","stable_key":"3b71c9a2-e2fe-5ab8-a85b-15ae1be836dd:silica-uptake-block-2014","predicate":"preserves_release","statement":"Low-dose cytochalasin D blocked silica engulfment while preserving caspase-1 processing and IL-1 beta release.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"bc6c6ec7-1b1e-54c3-b28f-12f664a5a621","mechanism_event_label":"Surface-associated crystals could still trigger a response when uptake was blocked.","subject":{"id":"3665c556-6afe-506a-b262-1c6dbae15244","slug":"mouse-low-dose-cytod-silica","display_name":"Low-dose cytochalasin D in the 2014 silica study","entity_type_key":"cellular_process"},"object":{"id":"c17455e2-5805-55e7-9ecc-09c953115c84","slug":"mouse-il1b","display_name":"Mouse IL-1 beta","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"bc6c6ec7-1b1e-54c3-b28f-12f664a5a621","stable_key":"3b71c9a2-e2fe-5ab8-a85b-15ae1be836dd:silica-uptake-block-2014-event","event_type":"observed_relationship","label":"Surface-associated crystals could still trigger a response when uptake was blocked.","description":"Low-dose cytochalasin D blocked silica engulfment while preserving caspase-1 processing and IL-1 beta release.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3665c556-6afe-506a-b262-1c6dbae15244","slug":"mouse-low-dose-cytod-silica","display_name":"Low-dose cytochalasin D in the 2014 silica study","entity_type_key":"cellular_process"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c17455e2-5805-55e7-9ecc-09c953115c84","slug":"mouse-il1b","display_name":"Mouse IL-1 beta","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"11b1cdb5-1b10-586b-9917-b4da18ac072f","slug":"silica","display_name":"Silica and soluble silicon","entity_type_key":"chemical_species"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"b2d4231b-3893-5d4e-8b52-d0effdaa26c9","slug":"crystalline-silica","display_name":"Crystalline silica / quartz particles","entity_type_key":"chemical_species"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"ae25f14e-2a54-5094-9952-a97b718f94a3","slug":"mouse-nlrp3","display_name":"Mouse NLRP3","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"69b5a136-93e3-567b-a97a-d33853229c81","slug":"mouse-casp1","display_name":"Mouse caspase-1","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"5165cee3-71fa-5248-ab5d-fefded3492c5","slug":"mouse-alveolar-silica-uptake","display_name":"Silica uptake in mouse alveolar macrophages","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse bone-marrow macrophages; 0.25–0.5 micromolar cytochalasin D.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Immobilized epoxy-crystal experiments used MSU, not silica; do not transfer that detail between materials.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"silica","display_name":"Silica and soluble silicon","entity_type_key":"chemical_species"}},{"dimension":"plain_language","value_text":"Surface-associated crystals could still trigger a response when uptake was blocked.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Activation of NLRP3 inflammasome by crystalline structures via cell surface contact. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25445147/ · DOI 10.1038/srep07281","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"98143603-96a3-556e-9ac1-c468cac40e0a","evidence_kind":"source_excerpt","locator":"Lines 464-470","start_line":464,"end_line":470,"excerpt":"## silica-uptake-block-2014\nSurface-associated crystals could still trigger a response when uptake was blocked.\nLow-dose cytochalasin D blocked silica engulfment while preserving caspase-1 processing and IL-1 beta release.\nModel: Mouse bone-marrow macrophages; 0.25–0.5 micromolar cytochalasin D.\nLimitations: Immobilized epoxy-crystal experiments used MSU, not silica; do not transfer that detail between materials.\nEvidence access: Primary full text\nActivation of NLRP3 inflammasome by crystalline structures via cell surface contact. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25445147/ · DOI 10.1038/srep07281","model_system":"Mouse bone-marrow macrophages; 0.25–0.5 micromolar cytochalasin D.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"dc4b461e-dd46-57ab-8213-8aeb7ff9e8d0","stable_key":"import-3b71c9a2-e2fe-5ab8-a85b-15ae1be836dd","title":"Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"e05d81962a1ca6cbfc68fce4fd3dbcdea67c8e61332c19f4fec5d0c3ab8bf1b9","revision_id":"6433ed49-a331-571b-a611-21e56c3ce4bc","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[{"id":"9cdfc2e2-c980-5a17-a93a-ca4ef9f07a3e","title":"Must silica be engulfed to activate the inflammasome?","kind":"contradiction","status":"open","why":"The 2008 study interprets inhibited uptake and cytokine release as evidence that phagocytosis is required. The 2014 study explicitly challenges that necessity using lower cytochalasin doses that block engulfment while preserving inflammatory output. This is a disputed mechanistic requirement, not a draft wording correction.","resolution":"Retain both results. Compare inhibitor concentration, actin-dependent functions beyond engulfment, crystal preparation, priming, potassium gradients and residual uptake. The later immobilized-crystal experiment used MSU and must not be mislabeled silica. Multiple activation routes are plausible but do not constitute a completed resolution.","created_at":"2026-09-19 14:07:52","record_type":"conflict","display_label":"Recorded conflict","record_url":"/conflicts/9cdfc2e2-c980-5a17-a93a-ca4ef9f07a3e","sides":[{"conflict_id":"9cdfc2e2-c980-5a17-a93a-ca4ef9f07a3e","ordinal":0,"label":"2008 uptake-dependent interpretation","revision_id":"6433ed49-a331-571b-a611-21e56c3ce4bc","start_line":432,"end_line":438,"quote":"## silica-uptake-block-2008\nBlocking engulfment also blocked inflammatory output in this experiment.\nCytochalasin D blocked silica uptake and IL-1 beta release, supporting a phagocytosis-dependent interpretation.\nModel: Mouse macrophages; related human PBMC result separately reported in the paper.\nLimitations: Inhibitor dose and non-uptake effects require comparison with later low-dose experiments. Correction record: A 2026 author correction replaces an erroneously duplicated lower-left Fig. 8c micrograph with the retrieved original. This is a figure correction, not a scientific contradiction or retraction. https://www.nature.com/articles/s41590-026-02468-9\nEvidence access: Primary full text\nSilica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18604214/ · DOI 10.1038/ni.1631","source_key":"import-3b71c9a2-e2fe-5ab8-a85b-15ae1be836dd","source_title":"Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19)","claim_ids":["06c28792-633c-5b65-8c53-2afe60d45826"]},{"conflict_id":"9cdfc2e2-c980-5a17-a93a-ca4ef9f07a3e","ordinal":1,"label":"2014 response despite uptake blockade","revision_id":"6433ed49-a331-571b-a611-21e56c3ce4bc","start_line":464,"end_line":470,"quote":"## silica-uptake-block-2014\nSurface-associated crystals could still trigger a response when uptake was blocked.\nLow-dose cytochalasin D blocked silica engulfment while preserving caspase-1 processing and IL-1 beta release.\nModel: Mouse bone-marrow macrophages; 0.25–0.5 micromolar cytochalasin D.\nLimitations: Immobilized epoxy-crystal experiments used MSU, not silica; do not transfer that detail between materials.\nEvidence access: Primary full text\nActivation of NLRP3 inflammasome by crystalline structures via cell surface contact. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25445147/ · DOI 10.1038/srep07281","source_key":"import-3b71c9a2-e2fe-5ab8-a85b-15ae1be836dd","source_title":"Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19)","claim_ids":["3441e006-b6b4-561c-a22c-5489ba0c7513"]}]}],"corrections":[],"research":null}