{"id":"096b04f4-b183-5771-bb4a-025169704e24","stable_key":"104835a3-b891-5dc4-a6bb-42ab7c6f96c4:butyrate-ibd-hcar2-not-required","predicate":"modulates","statement":"GPR109A/G-protein inhibition did not remove the tested human monocyte/macrophage anti-inflammatory response to butyrate; HDAC3-related mechanisms were implicated.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"cb622525-85c4-533b-847b-49b4b9ec976a","mechanism_event_label":"A receptor important in some models was not required for this tested response.","subject":{"id":"e7428a7f-d35a-5406-9904-a88984814833","slug":"butyrate","display_name":"Butyrate","entity_type_key":"small_molecule"},"object":{"id":"2a8ca2a2-20ea-5f75-8070-85b24ff4ba16","slug":"human-butyrate-ibd-cytokines","display_name":"Cytokine output of butyrate-treated human IBD biopsies","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"cb622525-85c4-533b-847b-49b4b9ec976a","stable_key":"104835a3-b891-5dc4-a6bb-42ab7c6f96c4:butyrate-ibd-hcar2-not-required-event","event_type":"observed_relationship","label":"A receptor important in some models was not required for this tested response.","description":"GPR109A/G-protein inhibition did not remove the tested human monocyte/macrophage anti-inflammatory response to butyrate; HDAC3-related mechanisms were implicated.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e7428a7f-d35a-5406-9904-a88984814833","slug":"butyrate","display_name":"Butyrate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"2a8ca2a2-20ea-5f75-8070-85b24ff4ba16","slug":"human-butyrate-ibd-cytokines","display_name":"Cytokine output of butyrate-treated human IBD biopsies","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c31b5501-5abf-57bb-8324-15923ed678cf","slug":"hcar2","display_name":"Human hydroxycarboxylic acid receptor 2 / HCAR2","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"03ca3c36-ec13-5f8d-8a0b-f8744591ae37","slug":"hdac3","display_name":"Human histone deacetylase 3","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human monocytes and THP-1 macrophage experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This does not negate the distinct mouse epithelial IL-18 dependency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"butyrate","display_name":"Butyrate","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A receptor important in some models was not required for this tested response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Butyrate suppresses mucosal inflammation in inflammatory bowel disease primarily through HDAC3 inhibition in monocytes and macrophages. · 2025 · https://pubmed.ncbi.nlm.nih.gov/41110099/ · DOI 10.1111/febs.70289","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"7337a2eb-ba78-59a4-a1b3-186c3ffcb6d6","evidence_kind":"source_excerpt","locator":"Lines 430-436","start_line":430,"end_line":436,"excerpt":"## butyrate-ibd-hcar2-not-required\nA receptor important in some models was not required for this tested response.\nGPR109A/G-protein inhibition did not remove the tested human monocyte/macrophage anti-inflammatory response to butyrate; HDAC3-related mechanisms were implicated.\nModel: Human monocytes and THP-1 macrophage experiments.\nLimitations: This does not negate the distinct mouse epithelial IL-18 dependency.\nEvidence access: Primary abstract\nButyrate suppresses mucosal inflammation in inflammatory bowel disease primarily through HDAC3 inhibition in monocytes and macrophages. · 2025 · https://pubmed.ncbi.nlm.nih.gov/41110099/ · DOI 10.1111/febs.70289","model_system":"Human monocytes and THP-1 macrophage experiments.","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":"33205bb8-dcbe-5d2c-afca-86075d7748d1","stable_key":"import-104835a3-b891-5dc4-a6bb-42ab7c6f96c4","title":"Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"a1253eb4426fc45d7b7c113028aa4ba2e9f89a9653272f3795437fc222bad558","revision_id":"c2320e65-a252-57a9-8838-7abf3d23400e","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}