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人羊膜间充质干细胞条件培养基通过调节单核细胞中 CD14/TLR4 介导的信号通路抑制 LPS 诱导的细胞损伤和炎症。

Human amniotic mesenchymal stem cell-conditioned medium inhibited LPS-induced cell injury and inflammation by modulating CD14/TLR4-mediated signaling pathway in monocytes.

机构信息

The Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China; School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing 211166, China.

The Laboratory Center for Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China.

出版信息

Mol Immunol. 2023 Jun;158:10-21. doi: 10.1016/j.molimm.2023.04.009. Epub 2023 Apr 21.

Abstract

Human amniotic mesenchymal stem cells (hAMSCs) have attracted considerable attention as a promising regenerative therapy. Many studies reported that the conditioned medium of hAMSCs (AM-CM) exerted anti-inflammatory and immunomodulatory functions, while its underlying mechanism is poorly understood. In this study, we first confirmed that AM-CM (25%, 50%, 100%) was optimal for anti-inflammation at 24 h. Lipopolysaccharide (LPS)-induced alteration of cell morphology, the decrease of cell proliferation, and the upregulation of cell apoptosis were significantly reversed in AM-CM-treated THP-1 cells. 25% and 50% AM-CM significantly decreased LPS-induced intracellular reactive oxygen species (ROS) production and proinflammatory cytokines secretion. Mechanistically, we found that AM-CM treatment suppressed LPS-induced activation of MAPK and NF-κB pathways by inhibiting CD14/TLR4 in THP-1 cells. Meanwhile, activation of NLRP3 inflammasome was also dose-dependently attenuated by AM-CM treatment. Thus, AM-CM may exert positive influences on the inflammation microenvironment and provide a novel strategy for improving tissue regeneration.

摘要

人羊膜间充质干细胞(hAMSCs)作为一种有前途的再生治疗方法引起了相当大的关注。许多研究报告称,hAMSCs 的条件培养基(AM-CM)发挥了抗炎和免疫调节功能,但其潜在机制尚不清楚。在这项研究中,我们首先证实 AM-CM(25%、50%、100%)在 24 小时时最适合抗炎。AM-CM 处理的 THP-1 细胞中,脂多糖(LPS)诱导的细胞形态改变、细胞增殖减少和细胞凋亡上调得到了显著逆转。25%和 50%的 AM-CM 显著降低了 LPS 诱导的细胞内活性氧(ROS)产生和促炎细胞因子的分泌。从机制上讲,我们发现在 THP-1 细胞中,AM-CM 通过抑制 CD14/TLR4 抑制了 LPS 诱导的 MAPK 和 NF-κB 通路的激活。同时,AM-CM 处理也剂量依赖性地减弱了 NLRP3 炎性小体的激活。因此,AM-CM 可能对炎症微环境产生积极影响,并为改善组织再生提供新的策略。

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