{"id":"82813683-d43b-5681-88ef-c8e0a2d38907","stable_key":"research:txnip-nlrp3","predicate":"contributes_to","statement":"TXNIP contributes to NLRP3 activation in the metabolic/oxidative-stress settings tested by Zhou and colleagues.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"literature_reviewed:direct_experimental","direction":"context_dependent","is_public":true,"mechanism_event_id":"cd91df0c-3f17-51b9-8a88-841810ee83ba","mechanism_event_label":"TXNIP can help activate this inflammatory pathway in particular settings.","subject":{"id":"b67aad59-1bc7-5cfc-8644-3bcbcdc8f671","slug":"txnip","display_name":"TXNIP","entity_type_key":"protein"},"object":{"id":"b53e832d-0776-5495-b5cd-cb6a8e8c538b","slug":"nlrp3","display_name":"NLRP3","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"cd91df0c-3f17-51b9-8a88-841810ee83ba","stable_key":"research:txnip-nlrp3","event_type":"contextual_mechanism","label":"TXNIP can help activate this inflammatory pathway in particular settings.","description":"TXNIP contributes to NLRP3 activation in the metabolic/oxidative-stress settings tested by Zhou and colleagues.","status":"active","compartment":null,"participants":[{"entity":{"id":"b67aad59-1bc7-5cfc-8644-3bcbcdc8f671","slug":"txnip","display_name":"TXNIP","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b53e832d-0776-5495-b5cd-cb6a8e8c538b","slug":"nlrp3","display_name":"NLRP3","entity_type_key":"protein"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"cell_type","value_text":"Studied metabolic/inflammatory cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cellular and mouse metabolic/oxidative-stress models","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Other macrophage settings show Txnip-independent IL-1beta production.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Mus musculus and cell models","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"04b970bc-24c8-5cd8-84d6-a361d2a60a50","evidence_kind":"curated_literature_summary","locator":"lines 1360-1370","start_line":1360,"end_line":1370,"excerpt":"## txnip-nlrp3\n\nTXNIP can help activate this inflammatory pathway in particular settings.\n\nTXNIP contributes to NLRP3 activation in the metabolic/oxidative-stress settings tested by Zhou and colleagues.\n\nOrganism: Mus musculus and cell models\nCell type: Studied metabolic/inflammatory cells\nExperimental model: Cellular and mouse metabolic/oxidative-stress models\nLimitations: Other macrophage settings show Txnip-independent IL-1beta production.\nPrimary reference: [Thioredoxin-interacting protein links oxidative stress to inflammasome activation](https://pubmed.ncbi.nlm.nih.gov/20023662/)","model_system":"Cellular and mouse metabolic/oxidative-stress models","directness":"author_interpretation","verification_status":"secondary_verified","notes":"Curated summary; inspect the linked primary papers for original methods and results.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4f892f13-06ea-5199-a33c-a703f35c80ae","stable_key":"selenium-research-2026-09-17","title":"Selenium: literature corrections and mechanism additions","document_type":"curated_literature_review","citation_label":"Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually","file_path":"","sha256":"0b818b10c1c7120e5caf7f4d4019d7bd025d745692e424f515d3ef903c9ab7f3","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","review_status":"secondary_verified","notes":"Secondary curated summaries of primary experiments, with explicit models and limitations. Not archived primary full text."}}],"relations":[],"conflicts":[],"corrections":[{"id":"c4c894cb-324f-54d9-8f8d-d82fad4c8442","title":"TXNIP–NLRP3 is not a universal selenium-controlled switch","kind":"context_difference","status":"qualified","why":"TXNIP involvement in one setting coexists with Txnip-independent macrophage IL-1beta requiring Trx1 in another.","resolution":"Record stimulus, lineage and perturbation; do not automatically reverse TrxR1 loss into increased IL-1beta.","created_at":"2026-09-17 07:19:34","record_type":"qualification","display_label":"Source qualification","record_url":"/corrections/c4c894cb-324f-54d9-8f8d-d82fad4c8442","literature_review":{"revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1646,"end_line":1652,"papers":[{"paper_key":"zhou-2010","title":"Thioredoxin-interacting protein links oxidative stress to inflammasome activation","url":"https://pubmed.ncbi.nlm.nih.gov/20023662/","doi":"10.1038/ni.1831","year":2010,"model":"Cellular and mouse metabolic/oxidative-stress models","summary":"Supports context-specific TXNIP/NLRP3 link."},{"paper_key":"muri-2020","title":"Thioredoxin-1 distinctly promotes NF-kB target DNA binding and NLRP3 inflammasome activation independently of Txnip","url":"https://elifesciences.org/articles/53627","doi":"10.7554/eLife.53627","year":2020,"model":"Mouse macrophage gene perturbation/inflammasome experiments","summary":"Txnip-independent IL-1beta production can require Trx1 control of excessive ROS."}]},"sides":[{"conflict_id":"c4c894cb-324f-54d9-8f8d-d82fad4c8442","ordinal":0,"label":"Original preserved statement","revision_id":"fbed30e0-1c0d-5b83-8a1f-2867fbe8a5b5","start_line":244,"end_line":248,"quote":"TrxR1 (SELENOENZYME) keeps Trx1 reduced → keeps TXNIP sequestered → NLRP3 OFF\n\n```\n\n**Selenium deficiency → oxidized Trx1 → TXNIP released → IL-1β.** One selenoenzyme standing between redox state and the master inflammatory cytokine.","claim_id":null,"source_key":"immune","source_title":"Selenium in immune cells","claim_ids":[]},{"conflict_id":"c4c894cb-324f-54d9-8f8d-d82fad4c8442","ordinal":1,"label":"Original preserved statement","revision_id":"f8f97804-c1fb-56df-9c06-c02e36e2a5b8","start_line":388,"end_line":394,"quote":"Macrophage / inflammasome signaling\n\nThioredoxin, TXNIP, lipid peroxide and eicosanoid pathways provide plausible mechanisms\n\nCell/animal\n\nA useful summary is: selenium status can alter immune redox tone and cell survival, but no single immune-cell cascade explains all reported supplementation effects.","claim_id":null,"source_key":"deficiency","source_title":"Selenium deficiency: a mechanism-first reference","claim_ids":[]},{"conflict_id":"c4c894cb-324f-54d9-8f8d-d82fad4c8442","ordinal":2,"label":"Literature correction and experimental limits","revision_id":"80984e03-5f0f-5877-8094-afef7637444e","start_line":1646,"end_line":1652,"quote":"## TXNIP–NLRP3 is not a universal selenium-controlled switch\n\nTXNIP involvement in one setting coexists with Txnip-independent macrophage IL-1beta requiring Trx1 in another.\n\nRecord stimulus, lineage and perturbation; do not automatically reverse TrxR1 loss into increased IL-1beta.\nPrimary reference: [Thioredoxin-interacting protein links oxidative stress to inflammasome activation](https://pubmed.ncbi.nlm.nih.gov/20023662/)\nPrimary reference: [Thioredoxin-1 distinctly promotes NF-kB target DNA binding and NLRP3 inflammasome activation independently of Txnip](https://elifesciences.org/articles/53627)","claim_id":null,"source_key":"selenium-research-2026-09-17","source_title":"Selenium: literature corrections and mechanism additions","claim_ids":[]}]}],"research":{"topic":"Selenium scientific audit","plain_language":"TXNIP can help activate this inflammatory pathway in particular settings.","evidence_scope":"direct_experimental","papers":[{"key":"zhou-2010","title":"Thioredoxin-interacting protein links oxidative stress to inflammasome activation","url":"https://pubmed.ncbi.nlm.nih.gov/20023662/","doi":"10.1038/ni.1831","year":2010,"model":"Cellular and mouse metabolic/oxidative-stress models","summary":"Supports context-specific TXNIP/NLRP3 link."}]}}