{"id":"ff9b763a-0931-5eb8-a554-6f0da704a5d3","stable_key":"3b71c9a2-e2fe-5ab8-a85b-15ae1be836dd:silica-cholesterol-lysosome","predicate":"accumulation_reduces","statement":"U18666A-induced cholesterol accumulation reduced silica-induced inflammasome activation in mouse alveolar macrophages.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"50e9bfb3-f835-5550-8daf-4b84db754f38","mechanism_event_label":"Membrane-lipid handling can modify the response to particles.","subject":{"id":"d3a1b93d-0a2c-5d1b-b672-5e4ef4b09a10","slug":"cholesterol","display_name":"Cholesterol","entity_type_key":"lipid"},"object":{"id":"21e1d702-d09b-5bca-a3c6-3ca1fb27c3d8","slug":"mouse-silica-lysosomal-permeabilization","display_name":"Lysosomal permeabilization in silica-exposed mouse macrophages","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"50e9bfb3-f835-5550-8daf-4b84db754f38","stable_key":"3b71c9a2-e2fe-5ab8-a85b-15ae1be836dd:silica-cholesterol-lysosome-event","event_type":"observed_relationship","label":"Membrane-lipid handling can modify the response to particles.","description":"U18666A-induced cholesterol accumulation reduced silica-induced inflammasome activation in mouse alveolar macrophages.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d3a1b93d-0a2c-5d1b-b672-5e4ef4b09a10","slug":"cholesterol","display_name":"Cholesterol","entity_type_key":"lipid"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"21e1d702-d09b-5bca-a3c6-3ca1fb27c3d8","slug":"mouse-silica-lysosomal-permeabilization","display_name":"Lysosomal permeabilization in silica-exposed mouse macrophages","entity_type_key":"cellular_process"},"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":"6aa0ad36-6549-5c4a-9b2b-61ccd7ad446a","slug":"mouse-marco","display_name":"Mouse MARCO","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":"Pharmacologically altered lysosomal cholesterol handling.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Not evidence that raising blood cholesterol or dietary cholesterol protects the lung.","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":"Membrane-lipid handling can modify the response to particles.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Role of lysosomes in silica-induced inflammasome activation and inflammation in absence of MARCO. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25054161/ · DOI 10.1155/2014/304180","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"463bceb2-f771-5302-a535-75582b5bb555","evidence_kind":"source_excerpt","locator":"Lines 496-502","start_line":496,"end_line":502,"excerpt":"## silica-cholesterol-lysosome\nMembrane-lipid handling can modify the response to particles.\nU18666A-induced cholesterol accumulation reduced silica-induced inflammasome activation in mouse alveolar macrophages.\nModel: Pharmacologically altered lysosomal cholesterol handling.\nLimitations: Not evidence that raising blood cholesterol or dietary cholesterol protects the lung.\nEvidence access: Primary full text\nRole of lysosomes in silica-induced inflammasome activation and inflammation in absence of MARCO. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25054161/ · DOI 10.1155/2014/304180","model_system":"Pharmacologically altered lysosomal cholesterol handling.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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