{"id":"ab26a04c-8120-5504-a519-8738ba7541bf","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-sig-delta-ltb4-stimulus","predicate":"reduces-production-of","statement":"Delta-tocopherol at 50 µM inhibited LTB4 production stimulated by S1P or LPA in differentiated HL-60 cells, but did not inhibit the response to fMLP under the tested conditions.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"e4e8aa36-fa09-510d-bbad-bbb7471b6741","mechanism_event_label":"Delta-tocopherol reduced leukotriene output only for some ways of activating these cells.","subject":{"id":"4263af61-61c6-5295-b1d3-5ff25d057883","slug":"delta-tocopherol","display_name":"Delta-tocopherol","entity_type_key":"small_molecule"},"object":{"id":"64af5db1-ff09-5149-b084-96f79ab54faf","slug":"leukotriene-b4","display_name":"Leukotriene B4","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"e4e8aa36-fa09-510d-bbad-bbb7471b6741","stable_key":"e0ea2d6a-7429-5e9f-b774-41e5e3288da3:e-sig-delta-ltb4-stimulus-event","event_type":"biochemical_relationship","label":"Delta-tocopherol reduced leukotriene output only for some ways of activating these cells.","description":"Delta-tocopherol at 50 µM inhibited LTB4 production stimulated by S1P or LPA in differentiated HL-60 cells, but did not inhibit the response to fMLP under the tested conditions.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e359bc15-e675-5d83-b0fe-1d70814e130b","slug":"calcium-ion","display_name":"Calcium ion","entity_type_key":"ion"},"role":"signal involved in stimulus-dependent leukotriene activation","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"39f9446f-52a6-502d-b507-91137726f82c","slug":"arachidonic-acid","display_name":"AA","entity_type_key":"small_molecule"},"role":"leukotriene precursor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"4263af61-61c6-5295-b1d3-5ff25d057883","slug":"delta-tocopherol","display_name":"Delta-tocopherol","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"64af5db1-ff09-5149-b084-96f79ab54faf","slug":"leukotriene-b4","display_name":"Leukotriene B4","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"DMSO-differentiated human HL-60 neutrophil-like cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"10 min pretreatment; S1P 50 µM, LPA 100 µM or fMLP 1 µM for 10 min.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Stimulus specificity precludes a universal anti-inflammatory claim. High-dose lipid stimuli and transformed cells limit extrapolation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin E research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-e","display_name":"Vitamin E","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Delta-tocopherol reduced leukotriene output only for some ways of activating these cells.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[jiang2011] Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. (2011). https://pubmed.ncbi.nlm.nih.gov/21169551/ DOI: 10.4049/jimmunol.1002342","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Neutrophil-like leukemia-derived cell culture","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"6a1b9239-46a1-5b3a-b8b2-dcfc75e5125b","evidence_kind":"source_excerpt","locator":"Lines 881-892","start_line":881,"end_line":892,"excerpt":"### e-sig-delta-ltb4-stimulus\nDelta-tocopherol at 50 µM inhibited LTB4 production stimulated by S1P or LPA in differentiated HL-60 cells, but did not inhibit the response to fMLP under the tested conditions.\nCondition category: normal\nnutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Delta-tocopherol reduced leukotriene output only for some ways of activating these cells.\norganism: Homo sapiens\ntissue_or_cell_type: Neutrophil-like leukemia-derived cell culture\nexperimental_model: DMSO-differentiated human HL-60 neutrophil-like cells\nlimitations: Stimulus specificity precludes a universal anti-inflammatory claim. High-dose lipid stimuli and transformed cells limit extrapolation.\nexposure: 10 min pretreatment; S1P 50 µM, LPA 100 µM or fMLP 1 µM for 10 min.\ncross_nutrient: false\n[jiang2011] Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. (2011). https://pubmed.ncbi.nlm.nih.gov/21169551/ DOI: 10.4049/jimmunol.1002342","model_system":"DMSO-differentiated human HL-60 neutrophil-like cells","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [jiang2011] Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively. 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