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Biosci. (Landmark Ed)"],"abstract":"<jats:p>Background: Acute lung injury (ALI) significantly impacts the survival rates in intensive care units (ICU). Releasing a lot of pro-inflammatory mediators during the progression of the disease is a core feature of ALI, which may lead to uncontrolled inflammation and further damages the tissues and organs of patients. This study explores the potential therapeutic mechanisms of Dexmedetomidine (Dex) in ALI. Methods: In present study, cecal ligation puncture (CLP)-established ALI model mice and lipopolysaccharide (LPS)-stimulated RAW264.7 cell line were established to discover the influence of Dex. The evaluation of lung injury in vivo using histopathology, TUNEL assay, and analysis of inflammatory factors in bronchoalveolar lavage fluid (BALF) and serum. The receptor for advanced glycation end products (RAGE)\/Caspase-11-dependent pyroptosis-related proteins and macrophage polarization markers were analyzed using western blot, immunofluorescence, and flow cytometry. Finally, the mechanism of Dex in macrophages was further verified in vitro. Results: In vivo, Dex alleviated lung injury and decreased TUNEL-positive cell expression in CLP group. Dex decreased tumor necrosis factor-alpha (TNF-\u03b1), interleukin (IL)-6 and IL-17A levels in BALF and serum, while increasing IL-10 expression. Dex treatment decreased the protein levels of RAGE, caspase-11, IL-1\u03b2 and Gasdermin-D (GSDMD) in both in cells and in mice. Dex also down-regulated the synthesis of inducible nitric oxide synthase (iNOS) of classical activation phenotype (M1) markers, and up-regulated the synthesis of CD206 and Arg-1 of alternate activation phenotype (M2) markers. Conclusions: Dex treatment can inhibit inflammation and reduce lung injury caused by CLP. It could be associated with mediating M1 and M2 polarization and suppressing RAGE\/Caspase-11-depended pyroptosis.<\/jats:p>","DOI":"10.31083\/j.fbl2912409","type":"journal-article","created":{"date-parts":[[2024,12,30]],"date-time":"2024-12-30T11:37:01Z","timestamp":1735558621000},"source":"Crossref","is-referenced-by-count":7,"title":["Dexmedetomidine Mitigates Acute Lung Injury by Enhancing M2 Macrophage Polarization and Inhibiting RAGE\/Caspase-11-Mediated Pyroptosis"],"prefix":"10.31083","volume":"29","author":[{"given":"Yisi","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China"},{"name":"The Chongqing Key Laboratory of Translation Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kefeng","family":"Li","sequence":"first","affiliation":[{"name":"The Chongqing Key Laboratory of Translation Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China"},{"name":"Department of Critical Care Medicine, People's Hospital of Fengjie, 404600 Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuyang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Kuang","sequence":"first","affiliation":[{"name":"The Chongqing Key Laboratory of Translation Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China"},{"name":"Department of Critical Care Medicine, Dazu Hospital of Chongqing Medical University, 402360 Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihui","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, 400016 Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2024,12,3]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Clark E, Molnar AO, Joannes-Boyau O, Honor\u00e9 PM, Sikora L, Bagshaw SM. 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