Functional relevance of protein glycosylation to the pro-inflammatory effects of extracellular matrix metalloproteinase inducer (EMMPRIN) on monocytes/macrophages.
Functional relevance of protein glycosylation to the pro-inflammatory effects of extracellular matrix metalloproteinase inducer (EMMPRIN) on monocytes/macrophages.
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蛋白质糖基化与细胞外基质金属蛋白酶诱导剂（EMMPRIN）对单核细胞/巨噬细胞的促炎作用的功能相关性。
DOI：
10.1371/journal.pone.0117463
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
He B
中科院分区：
文献类型：
--
作者：
Ge H;Yuan W;Liu J;He Q;Ding S;Pu J;He B
细胞外基质金属蛋白酶诱导因子（EMMPRIN）是一种重要的促炎蛋白，参与单核/巨噬细胞的细胞功能。我们假设EMMPRIN蛋白糖基化的高水平异质性可能与其生物学效应具有功能相关性，并影响单核细胞/巨噬细胞的炎症活性。观察单核/巨噬细胞（THP-1细胞）表达的EMMPRIN在不同细胞外刺激下的糖基化模式，并鉴定不同糖基化形式的结构。在分别纯化高度糖基化和低度糖基化的蛋白质后，从各个方面检查不同糖基化形式对EMMPRIN的促炎作用的影响，例如细胞与内皮细胞的粘附、细胞迁移、细胞因子表达和炎症信号通路的激活。1)炎症信号（PMA和H2 O2）刺激后，EMMPRIN主要是高度糖基化的形式（HG-EMMPRIN）增加。2)单核细胞/巨噬细胞中EMMPRIN的糖基化导致N-连接聚糖被添加到蛋白质中，其中HG形式含有复合型聚糖，而糖基化程度较低的形式（LG）是简单型聚糖。3)只有HG-EMMPRIN而不是LG-EMMPRIN表现出促炎作用并刺激单核细胞/巨噬细胞的炎症活性（即，ERK 1/2和NF-κB通路的激活，单核细胞-内皮细胞粘附、细胞迁移和基质金属蛋白酶-9表达增强）。转录后糖基化是决定EMMPRIN在单核细胞/巨噬细胞中的生物学效应的重要机制。EMMPRIN的糖基化可能是调节单核/巨噬细胞炎症活性的潜在靶点。
Extracellular matrix metalloproteinase inducer (EMMPRIN) is an important pro-inflammatory protein involved in the cellular functions of monocytes/macrophages. We have hypothesized that high-level heterogeneousness of protein glycosylation of EMMPRIN may have functional relevance to its biological effects and affect the inflammatory activity of monocytes/macrophages. The glycosylation patterns of EMMPRIN expressed by monocytes/macrophages (THP-1 cells) in response to different extracellular stimuli were observed, and the structures of different glycosylation forms were identified. After the purification of highly- and less-glycosylated proteins respectively, the impacts of different glycosylation forms on the pro-inflammatory effects of EMMPRIN were examined in various aspects, such as cell adhesion to endothelial cells, cell migrations, cytokine expression, and activation of inflammatory signalling pathway. 1) It was mainly the highly-glycosylated form of EMMPRIN (HG-EMMPRIN) that increased after being exposed to inflammatory signals (PMA and H2O2). 2) Glycosylation of EMMPRIN in monocytes/macrophages led to N-linked-glycans being added to the protein, with the HG form containing complex-type glycans and the less-glycosylated form (LG) the simple type. 3) Only the HG-EMMPRIN but not the LG-EMMPRIN exhibited pro-inflammatory effects and stimulated inflammatory activities of the monocytes/macrophages (i.e., activation of ERK1/2 and NF-κB pathway, enhanced monocyte-endothelium adhesion, cell migration and matrix metalloproteinase -9 expression). Post-transcriptional glycosylation represents an important mechanism that determines the biological effects of EMMPRIN in monocytes/macrophages. Glycosylation of EMMPRIN may serve as a potential target for regulating the inflammatory activities of monocytes/macrophages.
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影响因子：
15.9
作者：
GALIS, ZS;SUKHOVA, GK;LIBBY, P
通讯作者：
LIBBY, P
影响因子：
9
作者：
通讯作者：
--
DOI：
10.1161/01.atv.0000021411.53577.1c
发表时间：
2002-07-01
影响因子：
8.7
作者：
Major, TC;Liang, L;Bocan, TMA
通讯作者：
Bocan, TMA
影响因子：
4.8
作者：
Narizhneva, NV;Razorenova, OV;Byzova, TV
通讯作者：
Byzova, TV
DOI：
10.1073/pnas.92.17.7686
发表时间：
1995-08-15
影响因子：
11.1
作者：
DUDLEY, DT;PANG, L;SALTIEL, AR
通讯作者：
SALTIEL, AR