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Gr-1highLy6G+Myeloid-derived suppressor cells and their role in a murine model of non-alcoholic steatohepatitis

机译:Gr-1highLy6G +骨髓源性抑制细胞及其在非酒精性脂肪性肝炎小鼠模型中的作用

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摘要

Background and Aim: Myeloid-derived suppressor cells are a heterogeneous cell population that expand during several pathogenic conditions. However, their role in non-alcoholic steatohepatitis remains unclear. This study aimed to examine the systemic effects of myeloid-derived suppressor cells, to determine the role of Gr-1 Ly6G MDSCs and their correlation with the CXCL12/CXCR4 axis in non-alcoholic steatohepatitis. Methods: We established a non-alcoholic steatohepatitis model and detected inflammatory factors IL-6, PGE2, and INF-γ, using an enzyme-linked immunosorbent assay. Proportions of lymphocyte subsets in peripheral blood, CD11b Gr-1 myeloid-derived suppressor cells and its subsets in the blood, spleen, liver, and bone marrow were identified using flow cytometry. Adoptive transfer and depletion experiments for MDSCs were performed. Immunohistochemistry, migration assays, and experiments were used to analyze the role of CXCL12/CXCR4 in non-alcoholic steatohepatitis. Results: The proportion of CD11b Gr-1 MDSCs changed in the bone marrow, spleen, blood, and liver in the non-alcoholic steatohepatitis model. CD4+ and CD8+ T lymphocytes were significantly reduced in non-alcoholic steatohepatitis. Compared with control mice, a significant decrease in ALT and AST levels was observed in Gr-1 Ly6G MDSCs-treated model mice. The migration ability of AMD3100-treated MDSCs was significantly reduced, but was restored as CXCL12 levels increased. CXCL12 and CXCR4 protein levels increased significantly in the non-alcoholic steatohepatitis livers. Conclusions: Exogenous Gr-1 Ly6G MDSCs improved liver function during non-alcoholic steatohepatitis. The CXCR4/CXCL12 axis could be the key pathway mediating the attraction of myeloid-derived suppressor cells into the non-alcoholic steatohepatitis environment in mice.
机译:背景与目的:髓样来源的抑制细胞是异质细胞群,在几种致病条件下会扩增。然而,它们在非酒精性脂肪性肝炎中的作用仍不清楚。这项研究旨在检查骨髓来源的抑制细胞的全身作用,以确定在非酒精性脂肪性肝炎中Gr-1 Ly6G MDSC的作用及其与CXCL12 / CXCR4轴的相关性。方法:我们建立了一种非酒精性脂肪性肝炎模型,并使用酶联免疫吸附法检测了炎性因子IL-6,PGE2和INF-γ。使用流式细胞仪鉴定外周血淋巴细胞亚群,CD11b Gr-1髓样抑制细胞及其在血液,脾脏,肝脏和骨髓中的亚群的比例。对MDSC进行过继转移和耗竭实验。免疫组织化学,迁移测定和实验被用来分析CXCL12 / CXCR4在非酒精性脂肪性肝炎中的作用。结果:在非酒精性脂肪性肝炎模型中,CD11b Gr-1 MDSCs在骨髓,脾脏,血液和肝脏中的比例发生了变化。在非酒精性脂肪性肝炎中,CD4 +和CD8 + T淋巴细胞明显减少。与对照小鼠相比,在用Gr-1 Ly6G MDSCs处理的模型小鼠中观察到ALT和AST水平显着降低。经AMD3100处理的MDSC的迁移能力显着降低,但随着CXCL12水平的提高而恢复。在非酒精性脂肪性肝炎肝脏中,CXCL12和CXCR4蛋白水平显着增加。结论:外源性Gr-1 Ly6G MDSCs可改善非酒精性脂肪性肝炎期间的肝功能。 CXCR4 / CXCL12轴可能是介导小鼠髓样来源的抑制细胞进入非酒精性脂肪性肝炎环境的关键途径。

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