Enhancement Effects of Lysophospholipids on ICAM-1, IL-8 and MCP-1 Expression on Human Endothelial Cell

水解磷酸脂誘導人類內皮細胞黏著因子ICAM-1與趨化因子IL-8，MCP-1表達之研究

林紀佑(Chi-Iou Lin) ； 李心予(Hsin-Yu Lee)

《Acta Zoologica Taiwanica》 14卷2期 (2004/10) Pp. 111-112

https://doi.org/10.6576/AZT.2004.14.(2).11

摘要

水解磷酸脂Lysophosphotidic Acid (LPA)與Sphingosine 1-Phsophate (S1P)均爲低分子量之脂肪酸，辨識細胞膜上Edg族受器進而調控細胞各項生理活性。本研究目的在探討水解磷酸脂於人類內皮細胞中對細胞黏著因子ICAM-1與趨化因子IL-8和MCP-1表現的影響。在human umbilical cord vein endothelial cells(HUVECs)中，透過LPA與S1P處理均能夠誘導ICAM-1、IL-8與MCP-1的mRNA與蛋白質的表現，並且觀察到時間與劑量依賴的現象。利用前處理不同化學抑制劑，發現LPA與S1P誘導HUVEC表現ICAM-1是仲介Gi與NF-κB但不仲介rho。然而，LPA與S1P刺激HUVEC表現IL-8與MCP-1是仲介Gi、rho與NF-κB。在細胞黏著的實驗中，發現水解磷酸脂能夠增強單核球與內皮細胞之間的黏著。在ChemotaxisAssay的實驗中，發現LPA與S1P能夠增強內皮細胞的趨化活性與號召單核球的能力。此研究成果應可使我們對水解磷酸脂之生炎機制有進一步之了解。

關鍵字

水解磷酸脂 ； Lysophosphotidic Acid LPA ； Sphingosine 1-Phsophate S1P ； 內皮細胞 ； 黏著 ； 單核球

並列摘要

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. Both ligands activate multiple signaling pathways in a variety of cell types. We examined the impact of lyosophosphlipids on the expression of intercellular adhesion molecule-1 (ICAM-1), and on the production of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), in human umbilical cord vein endothelial cells (HUVECs). Incubation with both LPA and S1P enhanced ICAM-1, IL-8 and MCP-1 mRNA and protein expressions in HUVECs were in a dose- and time-dependent manner. By various chemical inhibitors, we found LPA and S1P enhanced ICAM-1 expression is through a Gi- and NF-κB-dependent and rho-independent mechanism. However, LPA and S1P enhanced IL-8 and MCP-1 expression is through a Gi-, rho- and NF-κB-dependen mechanism. In a static cell-cell adhesion assay system, pretreatment of LPL enhanced the adhesion between HUVECs and U937 cells, a human mononucleated cell line. In a chemotaxis assay system, results shows that LPL treatments do enhance chemotactic activity of endothelial cell and monocyte recruitment subsequently mediate through up-regulating IL-8 and MCP-1 protein secretion. These results might be contributable to precisely elucidate the LPLs modulated wound healing and inflammation.

並列關鍵字

lysophospholipid LPL ； Lysophosphotidic Acid LPA ； Sphingosine 1-Phsophate S1P ； endothelial cell ； adhesion ； monocyte