{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T08:43:06Z","timestamp":1777711386603,"version":"3.51.4"},"reference-count":34,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01-HL155116"],"award-info":[{"award-number":["R01-HL155116"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Int J Immunopathol Pharmacol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Sepsis is a life-threatening condition with high global morbidity and mortality. Citrullinated histone H3 (CitH3) has gained recognition as a significant biomarker for early sepsis diagnosis and management. This study aims to investigate the therapeutic potential of targeting both CitH3 and S100A8\/A9 to reduce sepsis-induced inflammation and organ damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Using a novel CitH3 antibody distinct from commercial options, we analyzed serum samples from LPS-treated mice through a co-immunoprecipitation assay followed by LC-MS\/MS proteomic analysis to explore the interaction between CitH3 and S100A8\/A9 proteins in peripheral blood. Additionally, in a Pseudomonas aeruginosa (PA)-induced lung injury model, we assessed CitH3 and S100A8\/A9 levels in bronchoalveolar lavage fluid (BALF), alveolar samples, and neutrophils to determine their influence on neutrophil activation and inflammatory responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Our study revealed, for the first time, that CitH3 and S100A8\/A9 synergistically promoted neutrophil activation, inflammatory responses, and NETosis, which exacerbated lung injury in sepsis. Dual targeting of CitH3 and S100A8\/A9 significantly reduced neutrophil recruitment, NETosis, and inflammation in the PA-induced lung injury model. This therapeutic approach improved lung injury and survival rates, accompanied by a shift in cytokine profiles, with reductions in pro-inflammatory cytokines and increases in anti-inflammatory cytokines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>These findings underscore the potential of dual targeting CitH3 and S100A8\/A9 as a novel therapeutic approach for sepsis. This combined intervention shows promising effects in reducing inflammation and enhancing survival, offering a groundbreaking strategy for sepsis diagnosis and treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03946320251338661","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T06:55:41Z","timestamp":1747724141000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Synergistic inhibition of CitH3 and S100A8\/A9: A novel therapeutic strategy for mitigating sepsis-induced inflammation and lung injury"],"prefix":"10.1177","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3359-6002","authenticated-orcid":false,"given":"Tao","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Michigan Health System, Ann Arbor, MI, USA"},{"name":"Department of Physiology, Xuzhou Medical University, Xuzhou, Jiangsu, 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