Scholarlink

Objective <p>Pulmonary inflammation is closely associated with macrophage polarization and lipid metabolic reprogramming. Miconazole (MCZ), traditionally used as an antifungal agent, exhibits emerging anti-inflammatory potential, yet its underlying mechanisms remain unclear.</p> Methods <p>A mouse model of lipopolysaccharide (LPS)-induced lung inflammation was employed to evaluate MCZ’s anti-inflammatory efficacy. In vivo inflammatory cell infiltration, cytokine expression (IL-6, IL-1β, TNF-α), and lung histopathology were assessed. Single-cell RNA sequencing (scRNA-seq) characterized alveolar macrophage subpopulations and associated lipid metabolism pathways. In vitro experiments with bone marrow-derived macrophages (BMDM) validated the changes of macrophage polarization.</p> Results <p>MCZ treatment significantly alleviated lung inflammation by decreasing inflammatory cell infiltration and suppressing pro-inflammatory cytokines. ScRNA-seq analysis revealed subcluster of <i>Itgam (Cd11b)</i> negative, <i>Mrc1</i>,<i> Marco</i>, and <i>Lgals3</i> high AMs, MCZ decreased the proportions of pro-inflammatory neutrophils and macrophages, and promoted the phenotypic shift of alveolar macrophages from a pro-inflammatory subtype (AM1) to an anti-inflammatory subtype (AM2). Further cell-cell communication analysis showed that MCZ suppressed interactions between AM1 alveolar macrophages and neutrophils <i>via</i> TNF-TNFR, CCL3/5-CCR1, and CXCL1-CXCR2 signaling pathways. Mechanistically, MCZ inhibited lipid synthesis in AM1 alveolar macrophages while enhancing lipid catabolism in AM2 alveolar macrophages. In vitro studies using BMDM further confirmed that MCZ inhibited LPS-induced macrophage M1 polarization and lipid droplet accumulation marked by perilipin 3 (PLIN3), while promoting IL-4/IL-13-induced M2 polarization.</p> Conclusion <p>MCZ exerts therapeutic effects against pulmonary inflammation primarily by modulating macrophage polarization through lipid metabolic reprogramming, highlighting its promise as a novel therapeutic approach for inflammatory lung diseases.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Miconazole attenuates LPS-induced lung inflammation by modulating alveolar macrophage polarization via promoting lipid metabolic reprogramming

  • 期刊论文

  • 发表日期：

    2025年8月25日

查看全文
  • Huanwen Wu,
  • Qijiang Zhao,
  • Liangliang Dong,
  • Yuxin Wu,
  • Chengzhi Zheng,
  • Tongquan Wu,
  • Daqing Ma,
  • Yicheng Xie,
  • Yingshuo Wang

摘要

Objective

Pulmonary inflammation is closely associated with macrophage polarization and lipid metabolic reprogramming. Miconazole (MCZ), traditionally used as an antifungal agent, exhibits emerging anti-inflammatory potential, yet its underlying mechanisms remain unclear.

Methods

A mouse model of lipopolysaccharide (LPS)-induced lung inflammation was employed to evaluate MCZ’s anti-inflammatory efficacy. In vivo inflammatory cell infiltration, cytokine expression (IL-6, IL-1β, TNF-α), and lung histopathology were assessed. Single-cell RNA sequencing (scRNA-seq) characterized alveolar macrophage subpopulations and associated lipid metabolism pathways. In vitro experiments with bone marrow-derived macrophages (BMDM) validated the changes of macrophage polarization.

Results

MCZ treatment significantly alleviated lung inflammation by decreasing inflammatory cell infiltration and suppressing pro-inflammatory cytokines. ScRNA-seq analysis revealed subcluster of Itgam (Cd11b) negative, Mrc1, Marco, and Lgals3 high AMs, MCZ decreased the proportions of pro-inflammatory neutrophils and macrophages, and promoted the phenotypic shift of alveolar macrophages from a pro-inflammatory subtype (AM1) to an anti-inflammatory subtype (AM2). Further cell-cell communication analysis showed that MCZ suppressed interactions between AM1 alveolar macrophages and neutrophils via TNF-TNFR, CCL3/5-CCR1, and CXCL1-CXCR2 signaling pathways. Mechanistically, MCZ inhibited lipid synthesis in AM1 alveolar macrophages while enhancing lipid catabolism in AM2 alveolar macrophages. In vitro studies using BMDM further confirmed that MCZ inhibited LPS-induced macrophage M1 polarization and lipid droplet accumulation marked by perilipin 3 (PLIN3), while promoting IL-4/IL-13-induced M2 polarization.

Conclusion

MCZ exerts therapeutic effects against pulmonary inflammation primarily by modulating macrophage polarization through lipid metabolic reprogramming, highlighting its promise as a novel therapeutic approach for inflammatory lung diseases.