Lysophospholipids increase IL-8 and MCP-1 expressions in human umbilical cord vein endothelial cells through an IL-1-dependent mechanism
Article first published online: 22 JUN 2006
Copyright © 2006 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 99, Issue 4, pages 1216–1232, 1 November 2006
How to Cite
Lin, C. I., Chen, C.-N., Chen, J. H. and Lee, H. (2006), Lysophospholipids increase IL-8 and MCP-1 expressions in human umbilical cord vein endothelial cells through an IL-1-dependent mechanism. J. Cell. Biochem., 99: 1216–1232. doi: 10.1002/jcb.20963
- Issue published online: 24 OCT 2006
- Article first published online: 22 JUN 2006
- Manuscript Accepted: 16 MAR 2006
- Manuscript Received: 22 SEP 2005
- National Science Council, Taiwan. Grant Numbers: NSC90-2316-B-002-019, NSC91-2311-B-002-071, NSC92-2311-B-002-095
- Ministry of Education Program for Promoting Academic Excellence of Universities Grant. Grant Number: 91-BFA09-2-4
- endothelial cells
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.