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全球糖蛋白分析鉴定出内毒素耐受单核细胞的标志物和 GPR84 作为 TNFα 表达的调节剂。

Global analysis of glycoproteins identifies markers of endotoxin tolerant monocytes and GPR84 as a modulator of TNFα expression.

机构信息

Septomics Research Center, Jena University Hospital, Jena, Germany.

Jena University Hospital, Integrated Research and Treatment Center - Center for Sepsis Control and Care (CSCC), Jena, Germany.

出版信息

Sci Rep. 2017 Apr 12;7(1):838. doi: 10.1038/s41598-017-00828-y.

DOI:10.1038/s41598-017-00828-y
PMID:28404994
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5429802/
Abstract

Exposure of human monocytes to lipopolysaccharide (LPS) induces a temporary insensitivity to subsequent LPS challenges, a cellular state called endotoxin tolerance. In this study, we investigated the LPS-induced global glycoprotein expression changes of tolerant human monocytes and THP-1 cells to identify markers and glycoprotein targets capable to modulate the immunosuppressive state. Using hydrazide chemistry and LC-MS/MS analysis, we analyzed glycoprotein expression changes during a 48 h LPS time course. The cellular snapshots at different time points identified 1491 glycoproteins expressed by monocytes and THP-1 cells. Label-free quantitative analysis revealed transient or long-lasting LPS-induced expression changes of secreted or membrane-anchored glycoproteins derived from intracellular membrane coated organelles or from the plasma membrane. Monocytes and THP-1 cells demonstrated marked differences in glycoproteins differentially expressed in the tolerant state. Among the shared differentially expressed glycoproteins G protein-coupled receptor 84 (GPR84) was identified as being capable of modulating pro-inflammatory TNFα mRNA expression in the tolerant cell state when activated with its ligand Decanoic acid.

摘要

人类单核细胞暴露于脂多糖（LPS）会导致其对随后的 LPS 挑战暂时不敏感，这种细胞状态称为内毒素耐受。在这项研究中，我们研究了 LPS 诱导的耐受人单核细胞和 THP-1 细胞的全局糖蛋白表达变化，以鉴定能够调节免疫抑制状态的标志物和糖蛋白靶标。我们使用酰肼化学和 LC-MS/MS 分析，分析了 48 小时 LPS 时间过程中糖蛋白表达的变化。在不同时间点的细胞快照鉴定了单核细胞和 THP-1 细胞表达的 1491 种糖蛋白。无标记定量分析显示，分泌型或膜锚定糖蛋白的表达在 LPS 诱导下会发生短暂或持久的变化，这些糖蛋白来源于细胞内膜包裹的细胞器或质膜。单核细胞和 THP-1 细胞在耐受状态下差异表达的糖蛋白存在显著差异。在共同差异表达的糖蛋白中，G 蛋白偶联受体 84（GPR84）被鉴定为当其配体癸酸激活时，能够调节耐受细胞状态中的促炎 TNFα mRNA 表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/037c/5429802/e3a6b386071d/41598_2017_828_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/037c/5429802/09aed0a748c0/41598_2017_828_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/037c/5429802/9332a8641ca2/41598_2017_828_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/037c/5429802/50ab5648f014/41598_2017_828_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/037c/5429802/a44b330dc1ee/41598_2017_828_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/037c/5429802/bbac1464f4c5/41598_2017_828_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/037c/5429802/e3a6b386071d/41598_2017_828_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/037c/5429802/09aed0a748c0/41598_2017_828_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/037c/5429802/9332a8641ca2/41598_2017_828_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/037c/5429802/50ab5648f014/41598_2017_828_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/037c/5429802/a44b330dc1ee/41598_2017_828_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/037c/5429802/bbac1464f4c5/41598_2017_828_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/037c/5429802/e3a6b386071d/41598_2017_828_Fig6_HTML.jpg

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