{"id":"2296ad5a-3018-58f9-bfeb-4c6867e329b7","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-microglial-nrf2-dependence","predicate":"silencing_reduces","statement":"Nrf2 siRNA weakened fisetin suppression of nitric oxide and IL-6, but not TNF-alpha to the same extent, in LPS-treated mouse BV2 cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"a503fddd-e5a2-5951-b6cd-30747bfa0dac","mechanism_event_label":"Even inflammatory outputs had different dependencies.","subject":{"id":"95319607-3946-51b3-8235-400ec3223692","slug":"mouse-nfe2l2","display_name":"Mouse Nrf2 / Nfe2l2","entity_type_key":"protein"},"object":{"id":"75d73f65-417e-52eb-a2be-780763de7c78","slug":"mouse-bv2-fisetin-inflammatory-suppression","display_name":"Fisetin-associated suppression of inflammatory output in mouse BV2 cells","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"a503fddd-e5a2-5951-b6cd-30747bfa0dac","stable_key":"74ef5bba-ee14-531c-b1bf-d1f297c56bb6:fisetin-microglial-nrf2-dependence-event","event_type":"observed_relationship","label":"Even inflammatory outputs had different dependencies.","description":"Nrf2 siRNA weakened fisetin suppression of nitric oxide and IL-6, but not TNF-alpha to the same extent, in LPS-treated mouse BV2 cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"95319607-3946-51b3-8235-400ec3223692","slug":"mouse-nfe2l2","display_name":"Mouse Nrf2 / Nfe2l2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"75d73f65-417e-52eb-a2be-780763de7c78","slug":"mouse-bv2-fisetin-inflammatory-suppression","display_name":"Fisetin-associated suppression of inflammatory output in mouse BV2 cells","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"dee05061-c3f3-5226-8054-dd58b76a585d","slug":"fisetin","display_name":"Fisetin","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"59d6d1cd-df32-5b58-b950-3188bc7b95d6","slug":"iron-ii","display_name":"Ferrous iron","entity_type_key":"ion"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; 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unverified.","entity":null}],"evidence":[{"id":"17747961-c38e-5f38-8c22-1466f8f1360e","evidence_kind":"source_excerpt","locator":"Lines 176-182","start_line":176,"end_line":182,"excerpt":"## fisetin-microglial-nrf2-dependence\nEven inflammatory outputs had different dependencies.\nNrf2 siRNA weakened fisetin suppression of nitric oxide and IL-6, but not TNF-alpha to the same extent, in LPS-treated mouse BV2 cells.\nModel: Mouse microglial cells; Nrf2 knockdown and metal comparisons.\nLimitations: Endpoint-specific response; not total suppression of immunity.\nEvidence access: Primary full text\nModulation of the Neuroprotective and Anti-inflammatory Activities of the Flavonol Fisetin by the Transition Metals Iron and Copper. · 2020 · https://pubmed.ncbi.nlm.nih.gov/33187316/ · DOI 10.3390/antiox9111113","model_system":"Mouse microglial cells; Nrf2 knockdown and metal comparisons.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; 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