{"doi":"10.4049/jimmunol.180.4.2531","title":"HMGB1 Develops Enhanced Proinflammatory Activity by Binding to Cytokines","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>High mobility group box 1 protein (HMGB1), originally characterized as a nuclear DNA-binding protein, has also been described to have an extracellular role when it is involved in cellular activation and proinflammatory responses. In this study, FLAG-tagged HMGB1 was inducibly expressed in the presence of culture media with or without added IL-1β, IFN-γ, or TNF-α. HMGB1 purified from cells grown in culture media alone only minimally increased cytokine production by MH-S macrophages and had no effect on murine neutrophils. In contrast, HMGB1 isolated from cells cultured in the presence of IL-1β, IFN-γ, and TNF-α had enhanced proinflammatory activity, resulting in increased production of MIP-2 and TNF-α by exposed cells. IL-1β was bound to HMGB1 isolated from cells cultured with this cytokine, and purified HMGB1 incubated with recombinant IL-1β acquired proinflammatory activity. Addition of anti-IL-1β Abs or the IL-1 receptor antagonist to cell cultures blocked the proinflammatory activity of HMGB1 purified from IL-1β-exposed cells, indicating that such activity was dependent on interaction with the IL-1 receptor. These results demonstrate that HMGB1 acquires proinflammatory activity through binding to proinflammatory mediators, such as IL-1β.</jats:p>","journal":"The Journal of Immunology","year":2008,"id":605187,"datarank":0.8960714417803893,"base_score":5.973809611869261,"endowment":5.973809611869261,"self_citation_contribution":0.8960714417803893,"citation_network_contribution":0.0,"self_endowment_contribution":0.8960714417803893,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":392,"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":1553094,"name":"Jaroslaw Zmijewski","orcid":null,"position":1,"is_corresponding":false},{"id":169672,"name":"Zhiwei Xu","orcid":null,"position":2,"is_corresponding":false},{"id":305241,"name":"Edward Abraham","orcid":"0000-0002-4429-2389","position":3,"is_corresponding":false},{"id":1553093,"name":"Yonggang Sha","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"HMGB1 Develops Enhanced Proinflammatory Activity by Binding to Cytokines","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>High mobility group box 1 protein (HMGB1), originally characterized as a nuclear DNA-binding protein, has also been described to have an extracellular role when it is involved in cellular activation and proinflammatory responses. In this study, FLAG-tagged HMGB1 was inducibly expressed in the presence of culture media with or without added IL-1β, IFN-γ, or TNF-α. HMGB1 purified from cells grown in culture media alone only minimally increased cytokine production by MH-S macrophages and had no effect on murine neutrophils. In contrast, HMGB1 isolated from cells cultured in the presence of IL-1β, IFN-γ, and TNF-α had enhanced proinflammatory activity, resulting in increased production of MIP-2 and TNF-α by exposed cells. IL-1β was bound to HMGB1 isolated from cells cultured with this cytokine, and purified HMGB1 incubated with recombinant IL-1β acquired proinflammatory activity. Addition of anti-IL-1β Abs or the IL-1 receptor antagonist to cell cultures blocked the proinflammatory activity of HMGB1 purified from IL-1β-exposed cells, indicating that such activity was dependent on interaction with the IL-1 receptor. These results demonstrate that HMGB1 acquires proinflammatory activity through binding to proinflammatory mediators, such as IL-1β.</jats:p>","is_dataset_classified":null,"base_score":5.973809611869261,"endowment":5.973809611869261,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18250463","pmcid":null,"openalex_id":"https://openalex.org/W1490007860","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"HL 062221","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"GM 049222","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"HL 076206","title":null}],"total_grants":3,"fwci":27.1104,"citation_percentile":0.99885819,"influential_citations":0,"citation_trend":[{"year":2012,"count":30},{"year":2013,"count":32},{"year":2014,"count":31},{"year":2015,"count":26},{"year":2016,"count":15},{"year":2017,"count":18},{"year":2018,"count":21},{"year":2019,"count":17},{"year":2020,"count":15},{"year":2021,"count":14},{"year":2022,"count":9},{"year":2023,"count":13},{"year":2024,"count":10},{"year":2025,"count":5},{"year":2026,"count":4}],"oa_status":"bronze","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://journals.aai.org/jimmunol/article-pdf/180/4/2531/1258174/zim00408002531.pdf","host_type":"journal"},{"url":"https://journals.aai.org/jimmunol/article-pdf/180/4/2531/1258174/zim00408002531.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jimmunol/article-pdf/180/4/2531/62674445/zim00408002531.pdf","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.180.4.2531","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18250463","host_type":"repository"}],"fields_of_study":["Advanced Glycation End Products research","Immune Response and Inflammation","Neutrophil, Myeloperoxidase and Oxidative Mechanisms"],"mesh_terms":["Animals","Cell Line","Humans","Macrophage Activation","Neutrophils","Oligopeptides","Peptides","Protein Binding","Cytokines","Macrophages, Alveolar","Neutrophil Activation","Inflammation Mediators","HMGB1 Protein","Cell Line, Tumor","Mice"],"keywords":["Proinflammatory cytokine","HMGB1","Extracellular","Cytokine","Tumor necrosis factor alpha","Receptor","Cell culture","Recombinant DNA","Biology","Cell biology","Chemistry","Immunology","Inflammation","Biochemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T01:51:26.491416Z","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":[]}