人脐带间充质干细胞调节血管内皮细胞中 CD54 和 CD105 的表达并抑制川崎病中的炎症反应。
Human umbilical cord mesenchymal stem cells regulate CD54 and CD105 in vascular endothelial cells and suppress inflammation in Kawasaki disease.
机构信息
Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, China; Research Institute of Comparative Medicine, Nantong University, Nantong, 226001, Jiangsu Province, China.
Department of Pediatrics, Zhongda Hospital Southeast University, Nanjing, 210009, Jiangsu Province, China.
出版信息
Exp Cell Res. 2021 Dec 15;409(2):112941. doi: 10.1016/j.yexcr.2021.112941. Epub 2021 Nov 22.
OBJECTIVE
The objective was to evaluate the expression levels of CD31CD54 and CD31CD105 endothelial microparticles (EMPs) before and after intravenous immunoglobulin (IVIG) treatment of Kawasaki disease (KD). To explore the role of human umbilical cord mesenchymal stem cells (hucMSCs) in inhibiting endothelial inflammation in KD, the effects of hucMSCs on the expression of CD54 and CD105 in endothelial cells in KD were analyzed in vivo and in vitro.
METHODS
The concentrations of IL-1β and VEGF in the peripheral blood of KD or healthy children were detected, and the distributions of CD31CD54 and CD31CD105 EMPs in platelet-poor plasma (PPP) were analyzed by flow cytometry. Human umbilical vein endothelial cells (HUVECs) were first cocultured with the patients' peripheral blood mononuclear cells (PBMCs). Next, HUVECs were cocultured with hucMSCs after stimulation with inactivated serum from patients. Cell proliferation and migration activities were assessed, and the expression of CD54, CD105 and IL-1β was analyzed. In an in vivo study, hucMSCs were transplanted into KD mice. The locations and expression levels of CD54, CD105 and IL-1β in the heart tissues of mice were analyzed.
RESULTS
The levels of IL-1β and CD31CD54 EMPs were significantly higher before IVIG treatment and 2 weeks after treatment in KD patients (P < 0.01). However, the levels of VEGF and CD31CD105 EMPs increased significantly in KD only after IVIG treatment (P < 0.01). KD-inactivated serum stimulation combined with cocultivation of PBMCs can activate inflammation in HUVECs, leading to reduced cell proliferation and migration activities. Cocultivation also increased the expression of CD54 and decreased the expression of CD105 (P < 0.001). Cocultivation with hucMSCs can reverse these changes. Additionally, hucMSC transplantation downregulated the expression of IL-1β and CD54 and significantly upregulated the expression of CD105 in KD mice.
CONCLUSION
The expression levels of CD31CD54 and CD31CD105 EMPs showed inconsistent changes at different KD statuses, providing potential markers for clinical application. HucMSCs suppress inflammation and regulate the expression levels of CD54 and CD105 in vascular endothelial cells in KD, possibly providing a new basis for stem cell therapy for KD.
目的
评估静脉注射免疫球蛋白（IVIG）治疗川崎病（KD）前后 CD31CD54 和 CD31CD105 内皮细胞微颗粒（EMP）的表达水平。为了探讨人脐带间充质干细胞（hucMSCs）在抑制 KD 内皮炎症中的作用，分析了 hucMSCs 对 KD 内皮细胞中 CD54 和 CD105 表达的体内和体外影响。
方法
检测 KD 或健康儿童外周血中白细胞介素 1β（IL-1β）和血管内皮生长因子（VEGF）的浓度，并用流式细胞术分析血小板贫乏血浆（PPP）中 CD31CD54 和 CD31CD105 EMP 的分布。首先将人脐静脉内皮细胞（HUVEC）与患者的外周血单核细胞（PBMC）共培养。然后，在用患者失活血清刺激后，将 HUVEC 与 hucMSCs 共培养。评估细胞增殖和迁移活性，并分析 CD54、CD105 和 IL-1β 的表达。在体内研究中，将 hucMSCs 移植到 KD 小鼠中。分析小鼠心脏组织中 CD54、CD105 和 IL-1β 的位置和表达水平。
结果
KD 患者在 IVIG 治疗前和治疗后 2 周时，IL-1β 和 CD31CD54 EMP 的水平显著升高（P<0.01）。然而，只有在 KD 患者接受 IVIG 治疗后，VEGF 和 CD31CD105 EMP 的水平才显著升高（P<0.01）。KD 失活血清刺激与 PBMC 共培养可激活 HUVEC 炎症，导致细胞增殖和迁移活性降低。共培养还增加了 CD54 的表达，降低了 CD105 的表达（P<0.001）。与 hucMSCs 共培养可逆转这些变化。此外，hucMSC 移植可下调 KD 小鼠中 IL-1β 和 CD54 的表达，并显著上调 CD105 的表达。
结论
不同 KD 状态下 CD31CD54 和 CD31CD105 EMP 的表达水平显示出不一致的变化，为临床应用提供了潜在的标志物。hucMSCs 抑制 KD 中血管内皮细胞的炎症，并调节 CD54 和 CD105 的表达水平，可能为 KD 的干细胞治疗提供新的依据。
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