4.5 Article

Dose-dependent immunomodulatory effects of metformin on human neonatal monocyte-derived macrophages

期刊

CELLULAR IMMUNOLOGY
卷 377, 期 -, 页码 -

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2022.104557

关键词

Polarization; Bronchopulmonary dysplasia; Cord blood; Inflammation; Adverse effect

资金

  1. Shenzhen Science and Technology Inovation Committee [JCYJ20180306173125699, JCYJ20190809170009528]
  2. Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties [SZGSP009]

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This study investigates the immunomodulatory function of metformin in human macrophages and finds that low-dose metformin promotes the expansion of anti-inflammatory macrophages, while high-dose treatment exacerbates inflammation.
While the association of inflammation with bronchopulmonary dysplasia (BPD) has long been appreciated, M1 proinflammatory macrophage population is emerging as the key element in driving the BPD inflammatory environment. Previous study suggests that low-dose metformin elicits an anti-inflammatory response, possibly through modulating macrophages, to improve disease outcome in a rat BPD model. To investigate this concept further, we examined the dose-dependent immunomodulatory function of metformin directly on human macrophages derived from cord blood (CB) monocytes. We demonstrate that low-dose metformin promotes expansion of M2 anti-inflammatory macrophages, contrasted with high-dose treatment, which exacerbates inflammation by favoring M1 polarization and restricting M2 phenotype. These findings highlight that metformin hold immunomodulatory ability by regulating macrophage polarization in a dose-dependent manner, and only when applied at low dose, exhibiting potential for beneficial anti-inflammatory adjuvant in BPD setting.

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