BACKGROUND Macrophage polarization and reprogramming in the lung play a critical role in the initiation, development and progression of acute lung injury (ALI). Regulating the activation and differentiation of pulmonary macrophages may provide a potential therapeutic strategy to treat ALI. We previously developed a novel class of anti-inflammatory nanoparticles (P12) that can potently inhibit Toll-like receptor (TLR) signaling in macrophages. These bioactive nanodevices were made of gold nanoparticles (GNPs) coated with hexapeptides to not only ensure their physiological stability but also enable GNPs with TLR inhibitory activity. RESULTS In this study, using a lipopolysaccharide (LPS) induced ALI mouse model, we showed that P12 was able to alleviate lung inflammation and damage through reducing the infiltration of inflammatory cells and increasing the anti-inflammatory cytokine (IL-10) in the lung. These results prompted us to investigate possible macrophage polarization by P12. We first confirmed that P12 primarily targeted macrophages in the lung to exert anti-inflammatory activity. We then showed that P12 could drive the polarization of mouse bone marrow-derived macrophages (BMDMs) toward anti-inflammatory M2 phenotype. Interestingly, in the ALI mouse model, P12 was able to increase the alveolar M2 macrophages and reduce both the alveolar and interstitial M1 macrophages in the bronchoalveolar lavage fluid (BALF) and lung tissues. CONCLUSION This study demonstrated that peptide-coated GNPs could induce M2 macrophage polarization in vitro and in vivo to effectively regulate lung inflammation, protect lung from injuries and promote inflammation resolution. The ability of regulating macrophage polarization together with TLR inhibition made such a bioactive nanodevice a new generation of potent therapeutics to treat ALI.

中文翻译：

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肽包被的金纳米颗粒对巨噬细胞极化的操纵及其对急性肺损伤的保护作用。

背景技术肺中的巨噬细胞极化和重编程在急性肺损伤（ALI）的起始，发展和进展中起关键作用。调节肺巨噬细胞的活化和分化可能提供治疗ALI的潜在治疗策略。我们之前开发了新型的消炎纳米颗粒（P12），可以有效抑制巨噬细胞中的Toll样受体（TLR）信号传导。这些具有生物活性的纳米装置由包覆有六肽的金纳米颗粒（GNP）制成，不仅可以确保其生理稳定性，而且还可以使GNP具有TLR抑制活性。结果在这项研究中，使用脂多糖（LPS）诱导的ALI小鼠模型，我们发现P12能够通过减少炎症细胞的浸润并增加肺中的抗炎细胞因子（IL-10）减轻肺部炎症和损害。这些结果促使我们研究P12可能引起的巨噬细胞极化。我们首先证实，P12主要靶向肺中的巨噬细胞发挥抗炎活性。然后，我们表明P12可以驱动小鼠骨髓衍生的巨噬细胞（BMDMs）趋向于消炎M2型。有趣的是，在ALI小鼠模型中，P12能够增加肺泡M2巨噬细胞，并减少支气管肺泡灌洗液（BALF）和肺组织中的肺泡和间质M1巨噬细胞。结论这项研究表明，肽包裹的GNPs可以在体内和体外诱导M2巨噬细胞极化，从而有效调节肺部炎症，保护肺免受伤害并促进炎症消退。调节巨噬细胞极化和TLR抑制的能力使这种生物活性纳米器件成为新一代治疗ALI的有效疗法。