{"id":"3a08b274-be44-51e1-a015-fe70dcb15184","stable_key":"3b71c9a2-e2fe-5ab8-a85b-15ae1be836dd:silica-cathepsin-inhibitor","predicate":"partly_reduces_release","statement":"CA-074-Me reduced silica-triggered IL-1 beta release, supporting a cathepsin-sensitive step.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"dc0dbe97-b8c3-5856-af62-cdf92732771f","mechanism_event_label":"A lysosomal protease inhibitor reduced inflammatory output.","subject":{"id":"ef236c35-18f9-5b76-8f70-05790140c19c","slug":"mouse-ca074me-silica-treatment","display_name":"CA-074-Me treatment of silica-exposed mouse macrophages","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":"dc0dbe97-b8c3-5856-af62-cdf92732771f","stable_key":"3b71c9a2-e2fe-5ab8-a85b-15ae1be836dd:silica-cathepsin-inhibitor-event","event_type":"observed_relationship","label":"A lysosomal protease inhibitor reduced inflammatory output.","description":"CA-074-Me reduced silica-triggered IL-1 beta release, supporting a cathepsin-sensitive step.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ef236c35-18f9-5b76-8f70-05790140c19c","slug":"mouse-ca074me-silica-treatment","display_name":"CA-074-Me treatment of silica-exposed mouse macrophages","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":"97540283-6cc6-58f8-9091-48b19d734612","slug":"mouse-ctsb","display_name":"Mouse cathepsin B","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"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":5,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse macrophages; 10 micromolar CA-074-Me.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Pharmacology alone does not establish unique cathepsin B necessity. 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","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":"A lysosomal protease inhibitor reduced inflammatory output.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18604214/ · DOI 10.1038/ni.1631","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"1046a4a1-daa7-5de8-acd2-9eb904b12d33","evidence_kind":"source_excerpt","locator":"Lines 448-454","start_line":448,"end_line":454,"excerpt":"## silica-cathepsin-inhibitor\nA lysosomal protease inhibitor reduced inflammatory output.\nCA-074-Me reduced silica-triggered IL-1 beta release, supporting a cathepsin-sensitive step.\nModel: Mouse macrophages; 10 micromolar CA-074-Me.\nLimitations: Pharmacology alone does not establish unique cathepsin B necessity. 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","model_system":"Mouse macrophages; 10 micromolar CA-074-Me.","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. 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