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

J Cell Biochem. 2006 Nov 1;99(4):1216-32. doi: 10.1002/jcb.20963.


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 NFkappaB-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / pharmacology
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • Chemotaxis / drug effects
  • Endothelial Cells / cytology*
  • Endothelial Cells / drug effects*
  • Humans
  • Interleukin-1 / metabolism*
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Lysophospholipids / pharmacology*
  • Pertussis Toxin / pharmacology
  • Proline / analogs & derivatives
  • Proline / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sphingosine / analogs & derivatives
  • Sphingosine / pharmacology
  • Thiocarbamates / pharmacology
  • Time Factors
  • Umbilical Veins / cytology*
  • Umbilical Veins / drug effects
  • Up-Regulation / drug effects
  • Vesicular Transport Proteins


  • Carrier Proteins
  • Chemokine CCL2
  • EXOC3 protein, human
  • Interleukin-1
  • Interleukin-8
  • Lysophospholipids
  • RNA, Messenger
  • Thiocarbamates
  • Vesicular Transport Proteins
  • prolinedithiocarbamate
  • sphingosine 1-phosphate
  • Proline
  • Pertussis Toxin
  • Sphingosine
  • lysophosphatidic acid