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

作者：Erridge Clett^*; Webb David J; Spickett Corinne M

来源：Atherosclerosis, 2007, 193(1): 77-85.

DOI：10.1016/j.atherosclerosis.2006.08.032

• inflammation
• atherosclerosis
• toll-like receptors
• oxidised phospholipids
• cell signalling

Objective: 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-snglycero-3-phosphorylcholine (OxPAPC) in the regulation of TLR 1, 2, 4 and 6 signalling.
Methods and results: Unlike established TLR agonists, OxPAPC did not induce NF-KB-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.
Conclusions: TLR4 signalling does not contribute to OxPAPC induced IL-8 expression in human epithelial HEK-293, monocytic THP- I 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.

• 出版日期2007-7