Objectives. Inflammatory disease characterized by clinical destructive respiratory disorder is called acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Studies have shown that luteolin exerts anti-inflammatory effects by increasing regulatory T cells (Tregs). In this study, we aimed to determine the effects of luteolin on ALI/ARDS and Treg differentiation. Methods. In this paper, we used cecal ligation puncture (CLP) to generate an ALI mouse model to determine the effects of luteolin on ALI/ARDS. Lung tissues were stained for interleukin- (IL-) 17A and myeloperoxidase (MPO) by immunohistochemical analysis. The levels of Treg-related cytokines in serum and bronchoalveolar lavage fluid (BALF) of mice were detected. The protein levels of NF-κB p65 in lung tissues were measured. Macrophage phenotypes in lung tissues were measured using immunofluorescence. The proportion of Tregs in splenic mononuclear cells and peripheral blood mononuclear cells (PBMCs) was quantified. Furthermore, in vitro, we evaluated the effects of luteolin on Treg differentiation, and the effects of IL-10 immune regulation on macrophage polarization were examined. Results. Luteolin alleviated lung injury and suppressed uncontrolled inflammation and downregulated IL-17A, MPO, and NF-κB in the lungs of CLP-induced mouse models. At this time, luteolin upregulated the level of IL-10 in serum and BALF and the frequency of CD4⁺CD25⁺FOXP3⁺ Tregs in PBMCs and splenic mononuclear cells of CLP mice. Luteolin treatment decreased the proportion of M1 macrophages and increased the proportion of M2 macrophages in lungs of CLP-induced mouse models. In vitro, administration of luteolin significantly induced Treg differentiation, and IL-10 promoted the polarization of M2 macrophages but reduced the polarization of M1 macrophages. Conclusions. Luteolin alleviated lung injury and suppressed uncontrolled inflammation by inducing the differentiation of CD4⁺CD25⁺FOXP3⁺ Tregs and upregulating the expression of IL-10. Furthermore, the anti-inflammatory cytokine IL-10 promoted polarization of M2 macrophages in vitro. Luteolin-induced Treg differentiation from naïve CD4⁺ T cells may be a potential mechanism for regulating IL-10 production.

中文翻译：

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木犀草素调节调节性 T 细胞的分化并激活 IL-10 依赖性巨噬细胞极化对抗急性肺损伤

目标。以临床破坏性呼吸系统疾病为特征的炎症性疾病称为急性肺损伤/急性呼吸窘迫综合征（ALI/ARDS）。研究表明，木犀草素通过增加调节性 T 细胞 (Tregs) 发挥抗炎作用。在这项研究中，我们旨在确定木犀草素对 ALI/ARDS 和 Treg 分化的影响。方法。在本文中，我们使用盲肠结扎穿刺 (CLP) 生成 ALI 小鼠模型，以确定木犀草素对 ALI/ARDS 的影响。通过免疫组织化学分析对肺组织进行白细胞介素 (IL-) 17A 和髓过氧化物酶 (MPO) 染色。检测小鼠血清和支气管肺泡灌洗液（BALF）中Treg相关细胞因子的水平。NF- κ的蛋白质水平测量肺组织中的B p65。使用免疫荧光测量肺组织中的巨噬细胞表型。量化了脾单核细胞和外周血单核细胞 (PBMC) 中 Tregs 的比例。此外，我们在体外评估了木犀草素对 Treg 分化的影响，并检查了 IL-10 免疫调节对巨噬细胞极化的影响。结果。在 CLP 诱导的小鼠模型的肺中，木犀草素减轻了肺损伤并抑制了不受控制的炎症并下调了 IL-17A、MPO 和 NF-κB 。此时木犀草素上调血清和BALF中IL-10的水平以及CD4 ⁺ CD25 ⁺ FOXP3 ^+的频率CLP 小鼠 PBMC 和脾单核细胞中的 Tregs。木犀草素处理降低了 CLP 诱导的小鼠模型肺中 M1 巨噬细胞的比例并增加了 M2 巨噬细胞的比例。在体外，给予木犀草素显着诱导Treg分化，IL-10促进M2巨噬细胞的极化但降低M1巨噬细胞的极化。结论。木犀草素通过诱导 CD4 ⁺ CD25 ⁺ FOXP3 ⁺ Tregs 的分化和上调 IL-10 的表达来减轻肺损伤并抑制不受控制的炎症。此外，抗炎细胞因子 IL-10在体外促进 M2 巨噬细胞的极化. 木犀草素诱导的 Treg 从幼稚 CD4 ⁺ T 细胞分化可能是调节 IL-10 产生的潜在机制。