Lysophospholipids increase IL-8 and MCP-1 expressions in human umbilical cord vein endothelial cells through an IL-1-dependent mechanism
Lysophospholipids increase IL-8 and MCP-1 expressions in human umbilical cord vein endothelial cells through an IL-1-dependent mechanism
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DOI：
10.1002/jcb.20963
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发表时间：
2006-11-01
影响因子：
4
通讯作者：
Lee, Hsinyu
中科院分区：
文献类型：
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作者：
Lin, Chi Iou;Chen, Chiung-Nien;Lee, Hsinyu
溶血磷脂酸（LPA）和1-磷酸鞘氨醇（S1 P）都是低分子量溶血磷脂（LPL）配体，其被G蛋白偶联受体（GPCR）的Edg家族识别。在内皮细胞中，这两种配体激活Edg受体，导致细胞增殖和细胞迁移。白细胞介素-8（IL-8）是一种C-X-C趋化因子，充当中性粒细胞的化学吸引物，而单核细胞化学吸引蛋白-1（MCP-1）是一种C-C趋化因子，主要充当单核细胞/巨噬细胞的化学吸引物。这两种因子都是由内皮细胞分泌的，并与导致动脉粥样硬化的过程有关。我们研究了LPL对IL-8和MCP-1表达的影响，IL-8和MCP-1是人脐带静脉内皮细胞（HUVECs）中白细胞募集的关键调节因子。结果表明，LPA和S1 P可促进IL-8和MCP-1 mRNA的表达，并以剂量和时间依赖的方式促进蛋白分泌。最大mRNA表达出现在配体处理后16小时。使用化学抑制剂的先前处理，LPL通过Gi-、Rho-和NF κ B依赖性机制增强IL-8和MCP-1表达。在趋化性测定系统中，内皮细胞的LPL处理通过上调IL-8和MCP-1蛋白分泌来增强单核细胞募集。IL-1受体拮抗剂AF 12198或IL-1功能阻断抗体预孵育均可抑制LPS诱导的HUVECs中IL-8和MCP-1 mRNA表达的增强效应。这些结果表明，由活化的血小板释放的LPL可能通过IL-1依赖性机制增强单核细胞对内皮细胞的IL-8和MCP-1依赖性化学吸引，这可能在促进伤口愈合和炎症过程中起重要作用。
Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are both low-molecular-weight lysophospholipid (LPL) ligands which are recognized by the Edg family of G protein-coupled receptors (GPCRs). in endothelial cells, these two ligands activate Edg receptors resulting in cell proliferation and cell migration. Interleukin-8 (IL-8) is a C-X-C chemokine and acts as a chemoattractant of neutrophils, whereas monocyte chemoattractant protein-1 (MCP-1) is a C-C chemokine and functions mainly as a chemoattractant of monocytes/macrophages. Both factors are secreted from endothelial cells and have been implicated in the processes leading to atherosclerosis. We examined the effects of LPLs on the expression of IL-8 and MCP-1, key regulators of leukocyte recruitment in human umbilical cord vein endothelial cells (HUVECs). Work illustrated in this article showed that LPA and S1P enhanced IL-8 and MCP-1 MRNA expressions, and protein secretions in dose- and time-dependent fashions. Maximal mRNA expression appeared at 16 hr post-ligand treatment. Using prior treatments with chemical inhibitors, LPLs enhanced IL-8 and MCP-l expressions through a Gi-, Rho-, and NF kappa B-dependent mechanism. In a chernotaxis assay system, LPL treatments of endothelial cells enhanced monocyte recruitment through upregulating IL-8 and MCP-l protein secretions. Pre-incubation with AF12198, an IL-1 receptor antagonist or IL-1 functional blocking antibody both suppressed the enhanced effects elicited by LPLs of IL-8 and MCP-l mRNA expressions in HUVECs. These results suggest that LPLs released by activated platelets might enhance the IL-8- and MCP-1-dependent chemoattraction of monocytes toward the endothelium through an IL-1-dependent mechanism, which may play an important role in facilitating wound-healing and inflammation processes.