title: Lysophospholipids increase IL-8 and MCP-1 expressions in human umbilical cord vein endothelial cells through an IL-1-dependent mechanism.
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 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.
authors.affiliation: Institute of Zoology, National Taiwan University, Taipei, Taiwan.
authors.forename: Chi Iou
authors.initials: CI
authors.lastname: Lin
authors.forename: Chiung-Nien
authors.initials: CN
authors.lastname: Chen
authors.forename: Jiun Hong
authors.initials: JH
authors.lastname: Chen
authors.forename: Hsinyu
authors.initials: H
authors.lastname: Lee
mesh_terms: D002352:Carrier Proteins / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology*; D037342:Pertussis Toxin / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology* / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D018932:Chemokine CCL2; C490685:EXOC3 protein, human; D007375:Interleukin-1; D016209:Interleukin-8; D008246:Lysophospholipids; D012333:RNA, Messenger; D013859:Thiocarbamates; D033921:Vesicular Transport Proteins; C066229:prolinedithiocarbamate; C060506:sphingosine 1-phosphate; D011392:Proline; D037342:Pertussis Toxin; D013110:Sphingosine; C032881:lysophosphatidic acid