{"doi":"10.3390/ijms25105360","title":"Gene Expression and Metabolome Analysis Reveals Anti-Inflammatory Impacts of 11,17diHDoPE on PM10-Induced Mouse Lung Inflammation","abstract":"<jats:p>Oxylipins, the metabolites of polyunsaturated fatty acids, are vital in regulating cell proliferation and inflammation. Among these oxylipins, specialized pro-resolving mediators notably contribute to inflammation resolution. Previously, we showed that the specialized pro-resolving mediators isomer 11,17dihydroxy docosapentaenoic acid (11,17diHDoPE) can be synthesized in bacterial cells and exhibits anti-inflammatory effects in mammalian cells. This study investigates the in vivo impact of 11,17diHDoPE in mice exposed to particulate matter 10 (PM10). Our results indicate that 11,17diHDoPE significantly mitigates PM10-induced lung inflammation in mice, as evidenced by reduced pro-inflammatory cytokines and pulmonary inflammation-related gene expression. Metabolomic analysis reveals that 11,17diHDoPE modulates inflammation-related metabolites such as threonine, 2-keto gluconic acid, butanoic acid, and methyl oleate in lung tissues. In addition, 11,17diHDoPE upregulates the LA-derived oxylipin pathway and downregulates arachidonic acid- and docosahexaenoic acid-derived oxylipin pathways in serum. Correlation analyses between gene expression and metabolite changes suggest that 11,17diHDoPE alleviates inflammation by interfering with macrophage differentiation. These findings underscore the in vivo role of 11,17diHDoPE in reducing pulmonary inflammation, highlighting its potential as a therapeutic agent for respiratory diseases.</jats:p>","journal":"International Journal of Molecular Sciences","year":2024,"id":619153,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"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":1597691,"name":"Dong-Hyuk Kim","orcid":"0009-0007-1469-839X","position":1,"is_corresponding":false},{"id":209631,"name":"Deok-Kun Oh","orcid":"0000-0002-6886-7589","position":2,"is_corresponding":false},{"id":762305,"name":"Ha Youn Shin","orcid":"0000-0002-8553-2107","position":3,"is_corresponding":false},{"id":289848,"name":"Choong Hwan Lee","orcid":"0000-0002-2311-185X","position":4,"is_corresponding":false},{"id":1479793,"name":"Uijin Kim","orcid":"0009-0001-9894-4362","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Gene Expression and Metabolome Analysis Reveals Anti-Inflammatory Impacts of 11,17diHDoPE on PM10-Induced Mouse Lung Inflammation","abstract":"<jats:p>Oxylipins, the metabolites of polyunsaturated fatty acids, are vital in regulating cell proliferation and inflammation. Among these oxylipins, specialized pro-resolving mediators notably contribute to inflammation resolution. Previously, we showed that the specialized pro-resolving mediators isomer 11,17dihydroxy docosapentaenoic acid (11,17diHDoPE) can be synthesized in bacterial cells and exhibits anti-inflammatory effects in mammalian cells. This study investigates the in vivo impact of 11,17diHDoPE in mice exposed to particulate matter 10 (PM10). Our results indicate that 11,17diHDoPE significantly mitigates PM10-induced lung inflammation in mice, as evidenced by reduced pro-inflammatory cytokines and pulmonary inflammation-related gene expression. Metabolomic analysis reveals that 11,17diHDoPE modulates inflammation-related metabolites such as threonine, 2-keto gluconic acid, butanoic acid, and methyl oleate in lung tissues. In addition, 11,17diHDoPE upregulates the LA-derived oxylipin pathway and downregulates arachidonic acid- and docosahexaenoic acid-derived oxylipin pathways in serum. Correlation analyses between gene expression and metabolite changes suggest that 11,17diHDoPE alleviates inflammation by interfering with macrophage differentiation. These findings underscore the in vivo role of 11,17diHDoPE in reducing pulmonary inflammation, highlighting its potential as a therapeutic agent for respiratory diseases.</jats:p>","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":"38791399","pmcid":"PMC11121355","openalex_id":"https://openalex.org/W4396890444","authors":[],"funders":[{"funder_name":"National Research Foundation of Korea","grant_id":"2020R1A4A1018648","title":null},{"funder_name":"National Research Foundation of Korea","grant_id":"2022R1F1A10733251220682073250102","title":null},{"funder_name":"National Research Foundation of Korea","grant_id":"2022M3H9A2082952","title":null}],"total_grants":3,"fwci":0.2168,"citation_percentile":0.53355867,"influential_citations":0,"citation_trend":[{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/25/10/5360/pdf?version=1715691564","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/25/10/5360/pdf?version=1715691564","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/25/10/5360/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms25105360","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38791399","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11121355","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11121355/pdf/ijms-25-05360.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11121355","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11121355?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Eicosanoids and Hypertension Pharmacology","Fatty Acid Research and Health","Inflammatory mediators and NSAID effects","Animals","Mice","Metabolome","Pneumonia","Particulate Matter","Anti-Inflammatory Agents","Fatty Acids, Unsaturated","Male","Lung","Mice, Inbred C57BL","Oxylipins","Metabolomics","Cytokines","Gene Expression Regulation"],"mesh_terms":["Animals","Anti-Inflammatory Agents","Fatty Acids, Unsaturated","Gene Expression Regulation","Lung","Male","Mice, Inbred C57BL","Pneumonia","Cytokines","Mice","Particulate Matter","Oxylipins","Metabolomics","Metabolome"],"keywords":["Inflammation","Oxylipin","Arachidonic acid","Docosahexaenoic acid","Metabolome","Biology","Docosapentaenoic acid","Proinflammatory cytokine","Lipid signaling","Lipoxin","Polyunsaturated fatty acid","In vivo","Chemistry","Metabolite","Biochemistry","Immunology","Fatty acid","Gene","Anti-inflammation","Metabolomics","particulate matter","Oxylipins","Pulmonary Inflammation","Macrophage Differentiation","Pro-resolving Mediators","Inflammatory Cytokine Genes"],"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":"2026-08-03T06:11:38.480279Z","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":[]}