Lysophospholipids increase IL-8 and MCP-1 expressions in human umbilical cord vein endothelial cells through an IL-1-dependent mechanism

Authors

  • Chi Iou Lin,

    1. Institute of Zoology, National Taiwan University, Taipei, Taiwan
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  • Chiung-Nien Chen,

    1. Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
    2. Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan
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  • Jiun Hong Chen,

    1. Institute of Zoology, National Taiwan University, Taipei, Taiwan
    2. Department of Life Science, National Taiwan University, Taipei, Taiwan
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  • Hsinyu Lee

    Corresponding author
    1. Institute of Zoology, National Taiwan University, Taipei, Taiwan
    2. Department of Life Science, National Taiwan University, Taipei, Taiwan
    3. Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan
    • Department of Life Science and Institute of Zoology, National Taiwan University, #1, Sec. 4, Roosevelt Road, Taipei, Taiwan 106.
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Abstract

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-1 expressions through a Gi-, Rho-, and NFκB-dependent mechanism. In a chemotaxis assay system, LPL treatments of endothelial cells enhanced monocyte recruitment through upregulating IL-8 and MCP-1 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-1 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. J. Cell. Biochem. 99: 1216–1232, 2006. © 2006 Wiley-Liss, Inc.

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