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Updated: Sep 10, 2025
Metabolic Characterization of Polarized M1 and M2 Bone Marrow-derived Macrophages Using Real-time Extracellular Flux Analysis
Published on: November 28, 2015
Miconazole attenuates LPS-induced lung inflammation by modulating alveolar macrophage polarization via promoting
Huanwen Wu1,2, Qijiang Zhao3, Liangliang Dong4
1Perioperative and Systems Medicine Laboratory, Department of Pulmonology, Laboratory Animal Center, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310052, China.
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.
