Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1197-1203
Published online before print May 29, 2003, doi: 10.1161/01.ATV.0000079340.80744.B8
Published online before print May 29, 2003, doi: 10.1161/01.ATV.0000079340.80744.B8
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© 2003 American Heart Association, Inc.
Vascular Biology |
Specific Phospholipid Oxidation Products Inhibit Ligand Activation of Toll-Like Receptors 4 and 2
From the Departments of Medicine (K.A.W., A.L.C., M.Y., G.S., R.M.L, J.N, D.K.V., J.A.B.), Pathology (K.A.W., M.Y., R.M.L, J.A.B.), and Microbiology and Immunology (S.R.K., R.L.M), University of California, Los Angeles; and the Department of Physiology (E.J.S.), University of Kentucky Medical School, Lexington.
Correspondence to Dr J.A. Berliner, UCLA, Box 951732, 13-229 CHS, Los Angeles, CA 90095-1732. E-mail JBerliner{at}mednet.ucla.edu
Objective— We have previously shown that phospholipid oxidation products of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC) inhibit lipopolysaccharide (LPS)-induced E-selectin expression and neutrophil binding in human aortic endothelial cells (HAECs). The current studies identify specific phospholipids that inhibit chemokine induction by Toll-like receptor-4 (TLR4) and -2 (TLR2) ligands in
ECs and macrophages.
Methods and Results— Measurements of interleukin (IL)-8 and monocyte chemotactic protein-1 levels secreted from ox-PAPC- and LPS-cotreated ECs indicate that ox-PAPC inhibits activation of TLR4 by LPS. The effects of IL-1ß and tumor necrosis factor-
, which utilize the same intracellular signaling molecules, were not inhibited. Cell fractionation and immunofluorescence analyses demonstrate that LPS induces membrane translocation of the LPS receptor complex to a lipid raft/caveolar fraction in ECs. Ox-PAPC inhibits this translocation and alters caveolin-1 distribution. Supporting an important role for caveolae in LPS action, overexpression of caveolin-1 enhanced LPS-induced IL-8 synthesis. Ox-PAPC also inhibits the effect of TLR2 and TLR4 ligands in human macrophages.
Conclusions— These studies report a novel mechanism that involves alterations to lipid raft/caveolar processing, by which specific phospholipid oxidation products inhibit activation by TLR4 and TLR2 ligands. These studies have broader implications for the role of ox-PAPC as a regulator of specific lipid raft/caveolar function.
Key Words: endothelial cells • oxidized phospholipids • lipopolysaccharide • Toll-like receptors • inflammation
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|
|
|
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|
|
|
|
|
|
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