{"doi":"10.4049/jimmunol.174.7.4345","title":"Molecular Circuits of Resolution: Formation and Actions of Resolvins and Protectins","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>The cellular events underlying the resolution of acute inflammation are not known in molecular terms. To identify anti-inflammatory and proresolving circuits, we investigated the temporal and differential changes in self-resolving murine exudates using mass spectrometry-based proteomics and lipidomics. Key resolution components were defined as resolution indices including Ψmax, the maximal neutrophil numbers that are present during the inflammatory response; Tmax, the time when Ψmax occurs; and the resolution interval (Ri) from Tmax to T50 when neutrophil numbers reach half Ψmax. The onset of resolution was at ∼12 h with proteomic analysis showing both haptoglobin and S100A9 levels were maximal and other exudate proteins were dynamically regulated. Eicosanoids and polyunsaturated fatty acids first appeared within 4 h. Interestingly, the docosahexaenoic acid-derived anti-inflammatory lipid mediator 10,17S-docosatriene was generated during the Ri. Administration of aspirin-triggered lipoxin A4 analog, resolvin E1, or 10,17S-docosatriene each either activated and/or accelerated resolution. For example, aspirin-triggered lipoxin A4 analog reduced Ψmax, resolvin E1 decreased both Ψmax and Tmax, whereas 10,17S-docosatriene reduced Ψmax, Tmax, and shortened Ri. Also, aspirin-triggered lipoxin A4 analog markedly inhibited proinflammatory cytokines and chemokines at 4 h (20–50% inhibition), whereas resolvin E1 and 10,17S-docosatriene’s inhibitory actions were maximal at 12 h (30–80% inhibition). Moreover, aspirin-triggered lipoxin A4 analog evoked release of the antiphlogistic cytokine TGF-β. These results characterize the first molecular resolution circuits and their major components activated by specific novel lipid mediators (i.e., resolvin E1 and 10,17S-docosatriene) to promote resolution.</jats:p>","journal":"The Journal of Immunology","year":2005,"id":601688,"datarank":0.981586776834719,"base_score":6.543911845564792,"endowment":6.543911845564792,"self_citation_contribution":0.981586776834719,"citation_network_contribution":0.0,"self_endowment_contribution":0.981586776834719,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":694,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":208607,"name":"Nan Chiang","orcid":null,"position":1,"is_corresponding":false},{"id":399212,"name":"Amiram Ariel","orcid":"0000-0002-7469-5728","position":2,"is_corresponding":false},{"id":112030,"name":"Makoto Arita","orcid":"0000-0001-9902-0463","position":3,"is_corresponding":false},{"id":1542846,"name":"Eric Tjonahen","orcid":null,"position":4,"is_corresponding":false},{"id":1542847,"name":"Katherine H Gotlinger","orcid":null,"position":5,"is_corresponding":false},{"id":436642,"name":"Song Hong","orcid":"0000-0002-3801-4147","position":6,"is_corresponding":false},{"id":1542848,"name":"Charles N Serhan","orcid":null,"position":7,"is_corresponding":false},{"id":1542845,"name":"Gerard L Bannenberg","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Molecular Circuits of Resolution: Formation and Actions of Resolvins and Protectins","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>The cellular events underlying the resolution of acute inflammation are not known in molecular terms. To identify anti-inflammatory and proresolving circuits, we investigated the temporal and differential changes in self-resolving murine exudates using mass spectrometry-based proteomics and lipidomics. Key resolution components were defined as resolution indices including Ψmax, the maximal neutrophil numbers that are present during the inflammatory response; Tmax, the time when Ψmax occurs; and the resolution interval (Ri) from Tmax to T50 when neutrophil numbers reach half Ψmax. The onset of resolution was at ∼12 h with proteomic analysis showing both haptoglobin and S100A9 levels were maximal and other exudate proteins were dynamically regulated. Eicosanoids and polyunsaturated fatty acids first appeared within 4 h. Interestingly, the docosahexaenoic acid-derived anti-inflammatory lipid mediator 10,17S-docosatriene was generated during the Ri. Administration of aspirin-triggered lipoxin A4 analog, resolvin E1, or 10,17S-docosatriene each either activated and/or accelerated resolution. For example, aspirin-triggered lipoxin A4 analog reduced Ψmax, resolvin E1 decreased both Ψmax and Tmax, whereas 10,17S-docosatriene reduced Ψmax, Tmax, and shortened Ri. Also, aspirin-triggered lipoxin A4 analog markedly inhibited proinflammatory cytokines and chemokines at 4 h (20–50% inhibition), whereas resolvin E1 and 10,17S-docosatriene’s inhibitory actions were maximal at 12 h (30–80% inhibition). Moreover, aspirin-triggered lipoxin A4 analog evoked release of the antiphlogistic cytokine TGF-β. These results characterize the first molecular resolution circuits and their major components activated by specific novel lipid mediators (i.e., resolvin E1 and 10,17S-docosatriene) to promote resolution.</jats:p>","is_dataset_classified":null,"base_score":6.543911845564792,"endowment":6.543911845564792,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15778399","pmcid":null,"openalex_id":"https://openalex.org/W1836416096","authors":[],"funders":[{"funder_name":"NIDCR NIH HHS","grant_id":"P50-DE016191","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"GM 38765","title":null},{"funder_name":"NIDCR NIH HHS","grant_id":"P0-1-DE 13499","title":null}],"total_grants":3,"fwci":13.4377,"citation_percentile":0.99389005,"influential_citations":0,"citation_trend":[{"year":2012,"count":43},{"year":2013,"count":58},{"year":2014,"count":36},{"year":2015,"count":37},{"year":2016,"count":38},{"year":2017,"count":47},{"year":2018,"count":36},{"year":2019,"count":34},{"year":2020,"count":47},{"year":2021,"count":29},{"year":2022,"count":29},{"year":2023,"count":26},{"year":2024,"count":18},{"year":2025,"count":15},{"year":2026,"count":5}],"oa_status":"bronze","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://journals.aai.org/jimmunol/article-pdf/174/7/4345/1199760/4345.pdf","host_type":"journal"},{"url":"https://journals.aai.org/jimmunol/article-pdf/174/7/4345/1199760/4345.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jimmunol/article-pdf/174/7/4345/62613585/4345.pdf","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.174.7.4345","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15778399","host_type":"repository"}],"fields_of_study":["Metabolomics and Mass Spectrometry Studies","Fatty Acid Research and Health","S100 Proteins and Annexins"],"mesh_terms":["Animals","Gene Expression Regulation","Haptoglobins","Inflammation","Lipids","Male","Mice, Inbred Strains","Neutrophils","Proteins","Mass Spectrometry","Eicosapentaenoic Acid","Eicosanoids","Calgranulin B","Mice"],"keywords":["Lipoxin","Lipid signaling","Lipidomics","Chemistry","Proinflammatory cytokine","Inflammation","Pharmacology","Biochemistry","Biology","Immunology","Receptor"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T17:07:57.352211Z","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":[]}