{"id":"d10ebea3-d088-5515-985e-80eb1f40f7e7","stable_key":"3b71c9a2-e2fe-5ab8-a85b-15ae1be836dd:silica-leupeptin-null","predicate":"does_not_prevent","statement":"Leupeptin reduced the measured cathepsin-B signal without preventing the nanoparticle-associated pyroptosis response.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"4f27c4b8-0415-5e37-99ae-ec6b633dfaa7","mechanism_event_label":"A protease-inhibitor result also failed to establish cathepsin B necessity.","subject":{"id":"e2525f1e-b784-5033-9dbc-44dddbdb98cc","slug":"leupeptin","display_name":"Leupeptin","entity_type_key":"small_molecule"},"object":{"id":"43ee9140-1e3a-5f52-9366-8548a402c78a","slug":"mouse-rawasc-pyroptosis","display_name":"Pyroptosis-associated response in mouse RAW-ASC cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"4f27c4b8-0415-5e37-99ae-ec6b633dfaa7","stable_key":"3b71c9a2-e2fe-5ab8-a85b-15ae1be836dd:silica-leupeptin-null-event","event_type":"observed_relationship","label":"A protease-inhibitor result also failed to establish cathepsin B necessity.","description":"Leupeptin reduced the measured cathepsin-B signal without preventing the nanoparticle-associated pyroptosis response.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e2525f1e-b784-5033-9dbc-44dddbdb98cc","slug":"leupeptin","display_name":"Leupeptin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"43ee9140-1e3a-5f52-9366-8548a402c78a","slug":"mouse-rawasc-pyroptosis","display_name":"Pyroptosis-associated response in mouse RAW-ASC cells","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":"c3377df7-792b-545f-aa2d-c6a67c4a4c01","slug":"silica-nanoparticles-2022-preparation","display_name":"Silica nanoparticles, 2022 RAW-ASC preparation","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 RAW-ASC cells; 1 microgram/mL leupeptin.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Leupeptin is not cathepsin-B-specific; measured abundance is not a selective genetic activity test.","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 protease-inhibitor result also failed to establish cathepsin B necessity.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Characterization of Cathepsin B in Mediating Silica Nanoparticle-Induced Macrophage Pyroptosis via an NLRP3-Dependent Manner. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35966002/ · DOI 10.2147/JIR.S371536","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b82dd40f-35f3-5711-b660-8583f06fdc01","evidence_kind":"source_excerpt","locator":"Lines 512-518","start_line":512,"end_line":518,"excerpt":"## silica-leupeptin-null\nA protease-inhibitor result also failed to establish cathepsin B necessity.\nLeupeptin reduced the measured cathepsin-B signal without preventing the nanoparticle-associated pyroptosis response.\nModel: Mouse RAW-ASC cells; 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