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比较蛋白质组学研究揭示了阻断白细胞介素 10(IL-10)及其受体抗体在人 U937 细胞中的增强免疫反应。

Comparative proteomic study reveals the enhanced immune response with the blockade of interleukin 10 with anti-IL-10 and anti-IL-10 receptor antibodies in human U937 cells.

机构信息

The First Affiliated Hospital/School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China.

Genecology Research Centre, University of the Sunshine Coast, Maroochydore DC, Australia.

出版信息

PLoS One. 2019 Mar 21;14(3):e0213813. doi: 10.1371/journal.pone.0213813. eCollection 2019.

Abstract

Blocking cytokine interleukin 10 (IL-10) at the time of immunisation enhances vaccine induced T cell responses and improves control of tumour cell growth in vivo. However, the effect of an IL-10 blockade on the biological function of macrophages has not been explored. In the current paper, a macrophage precursor cell line, U937 cells, was selected to investigate the differential expression of proteins and relevant cell signalling pathway changes, when stimulated with lipopolysaccharide (LPS) in the presence of antibodies to IL-10 or IL-10 receptor. We used a quantitative proteomic strategy to investigate variations in protein profiles of U937 cells following the treatments with LPS, LPS plus human anti-IL10 antibody and anti-IL10R antibody in 24hrs, respectively. The LPS treatment significantly activated actin-related cell matrix formation and immune response pathways. The addition of anti-IL10 and anti-IL10R antibody further promoted the immune response and potentially effect macrophage survival through PI3K/AKT signalling; however, the latter appeared to also upregulated oncogene XRCC5 and Cajal body associated processes.

摘要

在免疫接种时阻断细胞因子白细胞介素 10(IL-10)可增强疫苗诱导的 T 细胞反应,并改善体内肿瘤细胞生长的控制。然而,IL-10 阻断对巨噬细胞生物学功能的影响尚未得到探索。在目前的论文中,选择巨噬细胞前体细胞系 U937 细胞,研究在存在抗白细胞介素 10(IL-10)或 IL-10 受体抗体的情况下,用脂多糖(LPS)刺激时,蛋白质的差异表达和相关细胞信号通路变化。我们使用定量蛋白质组学策略来研究 LPS、LPS 加人抗 IL-10 抗体和抗 IL-10R 抗体处理后 U937 细胞蛋白谱在 24 小时内的变化。LPS 处理显著激活肌动蛋白相关细胞基质形成和免疫反应途径。添加抗 IL-10 和抗 IL-10R 抗体进一步促进了免疫反应,并通过 PI3K/AKT 信号通路潜在地影响巨噬细胞的存活;然而,后者似乎也上调了癌基因 XRCC5 和 Cajal 体相关过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1910/6428271/9abc1e658e6a/pone.0213813.g001.jpg

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