Toll-like receptor 4 signalling is neither sufficient nor required for oxidised phospholipids mediated induction of interleukin-8 expression

Erridge, Clett; Webb, David J. and Spickett, Corinne M. (2007). Toll-like receptor 4 signalling is neither sufficient nor required for oxidised phospholipids mediated induction of interleukin-8 expression. Atherosclerosis, 193 (1), pp. 77-85.

Abstract

Toll-like receptor (TLR)-4 signalling has been shown to accelerate atherosclerosis. As oxidised phospholipids are present in atherosclerotic plaque and have been shown to modulate TLR4 signalling, we investigated the role of oxidised 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (OxPAPC) in the regulation of TLR 1, 2, 4 and 6 signalling. Unlike established TLR agonists, OxPAPC did not induce NF-?B-dependent gene expression in monocytic THP-1 cells, human aortic endothelial cells or TLR-deficient HEK-293 cells transfected with TLRs 1, 2, 4 or 6. OxPAPC induction of IL-8 was not blocked by the TLR4 specific antagonist Rhodobacter sphaeroides LPS in human aortic endothelial cells, though OxPAPC potently inhibited TLR4 mediated IL-8 induction in these cells. OxPAPC upregulated IL-8 production in TLR4 deficient HEK-293 cells and this was not increased following TLR4 overexpression. Lipids extracted from carotid atherectomy samples did not stimulate TLR 1, 2, 4 or 6 signalling in a HEK-293 transfection assay. TLR4 signalling does not contribute to OxPAPC induced IL-8 expression in human epithelial HEK-293, monocytic THP-1 or aortic endothelial cells. As lipids extracted from diseased human artery also induced no TLR signalling, it is likely that the TLR-activating materials contributing to atherosclerosis are not of endogenous lipid origin.

Publication DOI: https://doi.org/10.1016/j.atherosclerosis.2006.08.032
Divisions: Life & Health Sciences > Biosciences
Uncontrolled Keywords: inflammation,cell signalling,atherosclerosis,toll-like receptors,oxidised phospholipids,Pharmacy and materia medica
Published Date: 2007-07

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