{"title":"Dexmedetomidine modulates peritoneal macrophage to attenuate lipopolysaccharide-induced inflammation","authors":"Tao Wang , Rui Pan , Jianli Wen , Xinglong Ma","doi":"10.1016/j.cellimm.2025.104942","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate how Dexmedetomidine (Dex) modulates the function of peritoneal macrophages (PMs) to reduce lipopolysaccharide (LPS)-induced inflammation.</div></div><div><h3>Methods</h3><div>The anti-inflammatory effect of Dex on LPS-stimulated PMs was assessed by examining its impact on their proliferation, phagocytosis, and polarization. Proliferation and phagocytic activity were measured using CCK-8 and Neutral Red staining assays, respectively. The levels of inflammatory mediators were quantified using ELISA. Additionally, macrophage polarization was evaluated via ELISA, flow cytometry, and Western blot analysis to identify shifts in macrophage phenotypes.</div></div><div><h3>Results</h3><div>Dex increased the proliferation and phagocytic capabilities of PMs, thereby mitigating LPS-induced inflammation. It suppressed pro-inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and high mobility group box 1 (HMGB1), while increasing levels of the anti-inflammatory cytokine interleukin-10 (IL-10). Furthermore, Dex promoted M2-type macrophage polarization, characterized by increased expression of IL-10, CD206, Arg-1, and CD11c. This effect was mediated through the JAK1/STAT6 signaling pathway, promoting M2 polarization, which was attenuated when JAK1 and STAT6 expression were downregulated.</div></div><div><h3>Conclusion</h3><div>Dex reduces LPS-induced inflammation in part by enhancing the proliferation, phagocytosis, and M2 polarization of PMs, with a key role for the JAK1/STAT6 pathway in promoting anti-inflammatory responses during sepsis.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"411 ","pages":"Article 104942"},"PeriodicalIF":3.7000,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0008874925000279","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的研究右美托咪定(Dex)如何调节腹腔巨噬细胞(PMs)的功能,以减轻脂多糖(LPS)诱导的炎症反应。增殖和吞噬活性分别用CCK-8和中性红染色法测定。炎症介质的水平用酶联免疫吸附法进行量化。此外,还通过 ELISA、流式细胞术和 Western 印迹分析评估了巨噬细胞的极化,以确定巨噬细胞表型的转变。它抑制了促炎介质,包括肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和高迁移率基团框 1(HMGB1),同时提高了抗炎细胞因子白细胞介素-10(IL-10)的水平。此外,Dex还能促进M2型巨噬细胞极化,其特征是IL-10、CD206、Arg-1和CD11c的表达增加。结论 德司能减轻LPS诱导的炎症,部分原因是它能增强巨噬细胞的增殖、吞噬能力和M2极化,而JAK1/STAT6通路在促进脓毒症期间的抗炎反应中起着关键作用。
Dexmedetomidine modulates peritoneal macrophage to attenuate lipopolysaccharide-induced inflammation
Purpose
To investigate how Dexmedetomidine (Dex) modulates the function of peritoneal macrophages (PMs) to reduce lipopolysaccharide (LPS)-induced inflammation.
Methods
The anti-inflammatory effect of Dex on LPS-stimulated PMs was assessed by examining its impact on their proliferation, phagocytosis, and polarization. Proliferation and phagocytic activity were measured using CCK-8 and Neutral Red staining assays, respectively. The levels of inflammatory mediators were quantified using ELISA. Additionally, macrophage polarization was evaluated via ELISA, flow cytometry, and Western blot analysis to identify shifts in macrophage phenotypes.
Results
Dex increased the proliferation and phagocytic capabilities of PMs, thereby mitigating LPS-induced inflammation. It suppressed pro-inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and high mobility group box 1 (HMGB1), while increasing levels of the anti-inflammatory cytokine interleukin-10 (IL-10). Furthermore, Dex promoted M2-type macrophage polarization, characterized by increased expression of IL-10, CD206, Arg-1, and CD11c. This effect was mediated through the JAK1/STAT6 signaling pathway, promoting M2 polarization, which was attenuated when JAK1 and STAT6 expression were downregulated.
Conclusion
Dex reduces LPS-induced inflammation in part by enhancing the proliferation, phagocytosis, and M2 polarization of PMs, with a key role for the JAK1/STAT6 pathway in promoting anti-inflammatory responses during sepsis.
期刊介绍:
Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered.
Research Areas include:
• Antigen receptor sites
• Autoimmunity
• Delayed-type hypersensitivity or cellular immunity
• Immunologic deficiency states and their reconstitution
• Immunologic surveillance and tumor immunity
• Immunomodulation
• Immunotherapy
• Lymphokines and cytokines
• Nonantibody immunity
• Parasite immunology
• Resistance to intracellular microbial and viral infection
• Thymus and lymphocyte immunobiology
• Transplantation immunology
• Tumor immunity.