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

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

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作者:Mei Li, Tenglong Li, Jianliang Jin, Chunfeng Xie, Jianyun Zhu

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.

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