The effective therapy for lung infectious diseases became more and more difficult since the severe antibiotic resistance of pathogenic microorganisms, it is urgent to develop new antimicrobial agents. Luteolin has been reported to play a crucial part in host immune responses. However, the clinical use of luteolin is impeded due to its hydrophobicity and low oral bioavailability. In this study, we formulated luteolin-loaded Methoxy poly(ethylene glycol)-poly(lactide) micelles (luteolin/MPEG-PLA), to improve the bioavailability of luteolin in lung infectious diseases. The results showed that luteolin/MPEG-PLA treatment could reduce the adhesion of Klebsiella pneumoniae (K. pneumoniae) to lung epithelial cells and enhance the germicidal ability of macrophages against K. pneumoniae compared to untreated group. Meanwhile, luteolin/MPEG-PLA showed stronger adhesion resistance of epithelial cells and germicidal ability of macrophages compared with free luteolin. In vivo study, luteolin/MPEG-PLA administration significantly promoted the clearance of bacteria and reduced inflammatory infiltration of lung tissue in K. pneumoniae induced lung infectious mice model. Further studies showed that treatment with luteolin/MPEG-PLA reduced the mRNA expression of LPS-induced inflammatory cytokines and chemokines in macrophages significantly. In general, luteolin/MPEG-PLA can enhance the anti-bacterial ability of lung epithelial cells and macrophages, and has a stronger therapeutic effect than free luteolin in bacterial-induced lung infection. Luteolin/MPEG-PLA may be an excellent potential drug for bacterial-induced lung infectious diseases treatment.

中文翻译：

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用纳米胶束改善木犀草素在细菌诱导的肺部感染中的抗炎作用。

由于病原微生物对抗生素的严重耐药性，肺部感染性疾病的有效治疗变得越来越困难，迫切需要开发新的抗菌药物。据报道，木犀草素在宿主免疫反应中起着至关重要的作用。然而，木犀草素因其疏水性和口服生物利用度低而阻碍了其临床应用。在这项研究中，我们配制了装载木犀草素的甲氧基聚（乙二醇）-聚（丙交酯）胶束（木犀草素/MPEG-PLA），以提高木犀草素在肺部感染性疾病中的生物利用度。结果表明木犀草素/MPEG-PLA处理可降低肺炎克雷伯菌（K.pneumoniae）对肺上皮细胞的粘附，增强巨噬细胞对肺炎克雷伯菌的杀菌能力与未治疗组相比。同时，与游离木犀草素相比，木犀草素/MPEG-PLA显示出更强的上皮细胞粘附抗性和巨噬细胞的杀菌能力。在体内研究中，木犀草素/MPEG-PLA 给药显着促进细菌清除并减少肺炎克雷伯菌肺组织的炎症浸润诱导肺感染小鼠模型。进一步的研究表明，木犀草素/MPEG-PLA 处理显着降低了巨噬细胞中 LPS 诱导的炎性细胞因子和趋化因子的 mRNA 表达。总的来说，木犀草素/MPEG-PLA可以增强肺上皮细胞和巨噬细胞的抗菌能力，在细菌性肺部感染中比游离木犀草素具有更强的治疗作用。木犀草素/MPEG-PLA 可能是治疗细菌性肺部感染疾病的极好潜在药物。