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

Abstract

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-sn-glycero-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-kappaB-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-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.

• Authors: Clett Erridge, David J Webb, Corinne M Spickett
• Journal: Atherosclerosis (Atherosclerosis) Vol. 193 Issue 1 Pg. 77-85 (Jul 2007) ISSN: 0021-9150 [Print] Ireland
• PMID: 16982060 (Publication Type: Journal Article)

Chemical References

• DNA Primers
• Interleukin-8
• Lipids
• NF-kappa B
• Phosphatidylcholines
• Recombinant Proteins
• TLR4 protein, human
• Toll-Like Receptor 4
• oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine

Topics

• Atherosclerosis (metabolism)
• Base Sequence
• Cell Line
• Cells, Cultured
• DNA Primers (genetics)
• Endothelial Cells (drug effects, metabolism)
• Gene Expression (drug effects)
• Humans
• Interleukin-8 (biosynthesis, genetics)
• Lipids (isolation & purification, pharmacology)
• NF-kappa B (metabolism)
• Phosphatidylcholines (pharmacology)
• Promoter Regions, Genetic
• Recombinant Proteins (genetics, metabolism)
• Signal Transduction (drug effects)
• Toll-Like Receptor 4 (genetics, metabolism)
• Transfection