{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:55:33Z","timestamp":1790988933999,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"vor","delay-in-days":737,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>This study aimed to investigate the therapeutic effects of recombinant human thrombomodulin (rhTM) on acute lung injury (ALI) caused by sepsis in rats. Rats that underwent cecal ligation and puncture (CLP) were treated with or without rhTM, and then mortality was analyzed. In another set of experiments, ALI was assessed. Furthermore, microthrombosis in the lungs was investigated by immunohistochemistry. Moreover, plasma inflammatory and anti-inflammatory cytokines, such as TNF-\u03b1, high-mobility group box chromosomal protein 1 (HMGB-1), and IL-10, were evaluated by ELISA. Production of TNF-\u03b1 and HMGB-1 by isolated tissue macrophages (M\u03c6s) was assessed in vitro. Mortality after CLP was significantly improved by rhTM treatment. In addition, rhTM treatment improved the wet\/dry weight ratio of the lungs, the pulmonary microvascular permeability, and the lung injury scores in animals that underwent CLP. Microthrombosis was detected in the lungs after CLP. These pathophysiological changes were blunted by rhTM treatment. Increased plasma TNF-\u03b1 and HMGB-1 levels were blunted by rhTM treatment; however, the anti-inflammatory cytokine IL-10 was significantly greater in the rhTM(+) group than in the rhTM(\u2212) group. Increased TNF-\u03b1 and HMGB-1 production by the tissue M\u03c6s stimulated with LPS were significantly blunted by rhTM treatment in vitro, but the production of IL-10 by the tissue M\u03c6s was not changed in the cells incubated with rhTM. Overall, rhTM improved the mortality caused by septic peritonitis. The possible mechanisms are most likely anti-inflammatory and anticoagulant effects, which lead to the prevention of ALI.<\/jats:p>","DOI":"10.4049\/immunohorizons.2200094","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T20:42:59Z","timestamp":1674852179000},"page":"159-167","source":"Crossref","is-referenced-by-count":5,"title":["Recombinant Human Thrombomodulin Reduces Mortality and Acute Lung Injury Caused by Septic Peritonitis in Rats"],"prefix":"10.1093","volume":"7","author":[{"given":"Hiroshi","family":"Kono","sequence":"first","affiliation":[{"name":"First Department of Surgery, Faculty of Medicine, University of Yamanashi , Yamanashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0483-3635","authenticated-orcid":false,"given":"Naohiro","family":"Hosomura","sequence":"additional","affiliation":[{"name":"First Department of Surgery, Faculty of Medicine, University of Yamanashi , Yamanashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetake","family":"Amemiya","sequence":"additional","affiliation":[{"name":"First Department of Surgery, Faculty of Medicine, University of Yamanashi , Yamanashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromichi","family":"Kawaida","sequence":"additional","affiliation":[{"name":"First Department of Surgery, Faculty of Medicine, University of Yamanashi , Yamanashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Furuya","sequence":"additional","affiliation":[{"name":"First Department of Surgery, Faculty of Medicine, University of Yamanashi , Yamanashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsutoshi","family":"Shoda","sequence":"additional","affiliation":[{"name":"First Department of Surgery, Faculty of Medicine, University of Yamanashi , Yamanashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Akaike","sequence":"additional","affiliation":[{"name":"First Department of Surgery, Faculty of Medicine, University of Yamanashi , Yamanashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"First Department of Surgery, Faculty of Medicine, University of Yamanashi , Yamanashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"First Department of Surgery, Faculty of Medicine, University of Yamanashi , Yamanashi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,27]]},"reference":[{"key":"2025010703544584300_r1","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.thromres.2011.10.013","article-title":"Sepsis, thrombosis and organ dysfunction","volume":"129","author":"Semeraro","year":"2012","journal-title":"Thromb. 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