{"id":"c4eaafb5-3946-5728-bff1-0f10665414db","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-pxr-tlr4-barrier","predicate":"loss_increases_permeability_via_context","statement":"Nr1i2-deficient mice had a barrier defect with increased TLR4-related signaling; additional Tlr4 deletion corrected the permeability phenotype.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e6627a50-a090-5b96-b6a9-9870ecb4fc3e","mechanism_event_label":"Receptor status and inflammatory sensing determined the barrier outcome.","subject":{"id":"10e4b201-804c-52c7-985a-1a7047f0cdc5","slug":"mouse-nr1i2","display_name":"Mouse pregnane X receptor / Pxr / Nr1i2","entity_type_key":"protein"},"object":{"id":"4509b8f7-cad2-57c3-84b4-75256713c083","slug":"mouse-trp-gut-permeability","display_name":"Mouse intestinal permeability in microbial tryptophan experiments","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e6627a50-a090-5b96-b6a9-9870ecb4fc3e","stable_key":"584c58f5-ab9f-53f3-97a9-55783db943b0:tryptophan-pxr-tlr4-barrier-event","event_type":"observed_relationship","label":"Receptor status and inflammatory sensing determined the barrier outcome.","description":"Nr1i2-deficient mice had a barrier defect with increased TLR4-related signaling; additional Tlr4 deletion corrected the permeability phenotype.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"10e4b201-804c-52c7-985a-1a7047f0cdc5","slug":"mouse-nr1i2","display_name":"Mouse pregnane X receptor / Pxr / Nr1i2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"4509b8f7-cad2-57c3-84b4-75256713c083","slug":"mouse-trp-gut-permeability","display_name":"Mouse intestinal permeability in microbial tryptophan experiments","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"769339cb-213b-559e-acc0-07ed00368b94","slug":"l-tryptophan","display_name":"L-Tryptophan","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"7a0caae0-e002-5310-b2cb-a45a1d62b11e","slug":"mouse-tlr4","display_name":"Mouse Toll-like receptor 4 / Tlr4","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"813fc8bf-f15a-5201-91e3-d1579084376d","slug":"indole-3-propionic-acid","display_name":"Indole-3-propionic acid / indolepropionate","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full text, genetic barrier experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Mouse Nr1i2 and Tlr4 genetic perturbations.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Does not demonstrate the same causal chain in human patients.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-tryptophan","display_name":"L-Tryptophan","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Receptor status and inflammatory sensing determined the barrier outcome.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25065623/ · DOI 10.1016/j.immuni.2014.06.014","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; 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