毛蕊异黄酮通过Spon2改善lps触发的MH-S肺泡巨噬细胞的炎症和M1巨噬细胞极化。

IF 2.5 4区 医学 Q3 CHEMISTRY, MEDICINAL
Gaoyan Chen, Xiaogang Li, Jingyi Zhang, Jiangli Ding, Yongchao Jiang, Rui Pan
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引用次数: 0

摘要

急性肺损伤(ALI)仍然是一种严重的炎症,治疗干预措施有限。本研究探讨了生物活性类黄酮毛萼异黄酮(calycosin, CAL)在脂多糖(LPS)诱导的h - s肺泡巨噬细胞细胞系中的抗炎潜力,并特别关注巨噬细胞极化机制。通过CCK-8细胞毒性评估和随后的实验分组(对照组、LPS和LPS + CAL),我们证明CAL能够在转录和蛋白质水平上显著抑制LPS触发的炎症介质,包括IL-1β、TNF-α和IL-6。流式细胞分析显示CAL对巨噬细胞极化标志物具有双重调节作用,下调m1相关的CD86,同时增强m2相关的CD206表达。转录组学分析鉴定出5,944个差异表达基因在lps刺激的细胞中富集TNF信号通路,而CAL处理特异性调节了83个主要参与TGF-β信号通路的基因。机制研究发现Spon2是关键的介质,cal诱导的Spon2下调可减轻炎症并促进M2极化,通过Spon2- shrna敲低和过表达实验证实了这一作用。值得注意的是,我们最近证明了Spon2过表达可以消除cal介导的TNF-α抑制和TGF-β/Smad2信号的激活。这些发现共同确立了CAL通过其spon2介导的巨噬细胞极化动力学调节作为ALI的有希望的治疗候选者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Calycosin ameliorates inflammation and M1 macrophage polarization via Spon2 in LPS-triggered MH-S alveolar macrophages.

Acute lung injury (ALI) remains a critical inflammatory condition with limited therapeutic interventions. This study explores the anti-inflammatory potential of calycosin (CAL), a bioactive flavonoid, in lipopolysaccharide (LPS)-induced MH-S alveolar macrophages cell line, with particular focus on macrophage polarization mechanisms. Through CCK-8 cytotoxicity assessment and subsequent experimental grouping (control, LPS, and LPS + CAL), we demonstrated CAL's ability to significantly suppress LPS-triggered inflammatory mediators including IL-1β, TNF-α, and IL-6 at both transcriptional and protein levels. Flow cytometric analysis revealed CAL's dual regulatory effect on macrophage polarization markers, downregulating M1-associated CD86 while enhancing M2-related CD206 expression. Transcriptomic profiling identified 5,944 differentially expressed genes in LPS-stimulated cells enriched in TNF signaling pathways, while CAL treatment specifically modulated 83 genes predominantly involved in TGF-β signaling. Mechanistic investigations identified Spon2 as a critical mediator, where CAL-induced Spon2 downregulation attenuated inflammation and promoted M2 polarization, effects corroborated through Spon2-shRNA knockdown and overexpression experiments. Notably, we newly demonstrate that Spon2 overexpression abolishes CAL-mediated suppression of TNF-α and activation of TGF-β/Smad2 signaling. These findings collectively establish CAL as a promising therapeutic candidate for ALI through its Spon2-mediated modulation of macrophage polarization dynamics.

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来源期刊
CiteScore
6.90
自引率
3.00%
发文量
79
审稿时长
1.7 months
期刊介绍: The Journal of Natural Medicines is an international journal publishing original research in naturally occurring medicines and their related foods and cosmetics. It covers: -chemistry of natural products -biochemistry of medicinal plants -pharmacology of natural products and herbs, including Kampo formulas and traditional herbs -botanical anatomy -cultivation of medicinal plants. The journal accepts Original Papers, Notes, Rapid Communications and Natural Resource Letters. Reviews and Mini-Reviews are generally invited.
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