{"doi":"10.4049/jimmunol.202.supp.183.17","title":"Leukotriene B4 is required for inflammasome activation","abstract":"<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>The events that initiate inflammatory responses during infections are not well understood. The lipid mediator leukotriene B4 (LTB4) is produced within seconds to minutes after phagocyte challenge and emerging evidence shown that LTB4 increases antimicrobial effector functions and inflammatory mediators, such as IL1b. Inflammasomes are intracellular platforms required for the secretion of IL1B/IL18 and an inflammatory cell death termed pyroptosis. Whether LTB4 enhances inflammasome-dependent IL1b secretion remains to be fully understood. Here, we hypothesize that LTB4 enhances inflammasome assembly and release of IL1b in macrophages during infection and sterile inflammation.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Methodology and Results</jats:title>\n                  <jats:p>To assess whether LTB4 is required for IL1b and pyroptosis in vivo, the skin of WT and LTB4R1−/− (BLT1) mice were infected with S. aureus for 24 h and biopsies were collected. To track inflammasome/IL1b production overtime, we treated IL1bDsRed mice as well as inflammasome reporter macrophages (ASC-cerulean) with a BLT1 antagonist. Using both genetic and pharmacological BLT1 blockage, we detected decreased IL1b production when compared to infected WT animals. A role for LTB4 in inflammasome activation was confirmed by detection of decreased caspase1 activation, ASC/NLRP3 assembly and gasdermin D (an initiator of pyroptosis) cleavage in vivo and in vitro in BLT1 deficient mice.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion</jats:title>\n                  <jats:p>Our data show that LTB4 is necessary for inflammasome activation and blocking BLT1 actions might be a broad and practical approach to inhibit inflammatory diseases induced by exaggerated inflammasome activation.</jats:p>\n               </jats:sec>","journal":"The Journal of Immunology","year":2019,"id":639339,"datarank":0.11783745791309803,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.013865380829106225,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.013865380829106225,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":585072,"name":"Stephanie Brandt","orcid":null,"position":1,"is_corresponding":false},{"id":1661001,"name":"Alexandra Ivo Medeiros","orcid":null,"position":2,"is_corresponding":false},{"id":1661003,"name":"Henrique Serezani","orcid":null,"position":3,"is_corresponding":false},{"id":1661000,"name":"Ana Salina","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Leukotriene B4 is required for inflammasome activation","abstract":"<jats:title>Abstract</jats:title>\n               <jats:sec>\n                  <jats:title>Background</jats:title>\n                  <jats:p>The events that initiate inflammatory responses during infections are not well understood. The lipid mediator leukotriene B4 (LTB4) is produced within seconds to minutes after phagocyte challenge and emerging evidence shown that LTB4 increases antimicrobial effector functions and inflammatory mediators, such as IL1b. Inflammasomes are intracellular platforms required for the secretion of IL1B/IL18 and an inflammatory cell death termed pyroptosis. Whether LTB4 enhances inflammasome-dependent IL1b secretion remains to be fully understood. Here, we hypothesize that LTB4 enhances inflammasome assembly and release of IL1b in macrophages during infection and sterile inflammation.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Methodology and Results</jats:title>\n                  <jats:p>To assess whether LTB4 is required for IL1b and pyroptosis in vivo, the skin of WT and LTB4R1−/− (BLT1) mice were infected with S. aureus for 24 h and biopsies were collected. To track inflammasome/IL1b production overtime, we treated IL1bDsRed mice as well as inflammasome reporter macrophages (ASC-cerulean) with a BLT1 antagonist. Using both genetic and pharmacological BLT1 blockage, we detected decreased IL1b production when compared to infected WT animals. A role for LTB4 in inflammasome activation was confirmed by detection of decreased caspase1 activation, ASC/NLRP3 assembly and gasdermin D (an initiator of pyroptosis) cleavage in vivo and in vitro in BLT1 deficient mice.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion</jats:title>\n                  <jats:p>Our data show that LTB4 is necessary for inflammasome activation and blocking BLT1 actions might be a broad and practical approach to inhibit inflammatory diseases induced by exaggerated inflammasome activation.</jats:p>\n               </jats:sec>","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19767382","pmcid":null,"openalex_id":"https://openalex.org/W4313382890","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2023,"count":1}],"oa_status":"closed","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://academic.oup.com/jimmunol/article/202/1_Supplement/183.17/7955993","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.202.supp.183.17","host_type":"journal"}],"fields_of_study":["Inflammasome and immune disorders","Urticaria and Related Conditions","IL-33, ST2, and ILC Pathways"],"mesh_terms":[],"keywords":["Inflammasome","Pyroptosis","Leukotriene B4","Secretion","Caspase 1","Inflammation","AIM2","In vivo","Chemistry","Cell biology","Biology","Immunology","Biochemistry","Biotechnology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T00:03:40.233799Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}