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

C. Erridge, D.J. Webb, C.M. Spickett

Research output: Contribution to journalArticle

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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-κB-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.
LanguageEnglish
Pages77-85
Number of pages9
JournalAtherosclerosis
Volume193
Issue number1
DOIs
Publication statusPublished - 2007

Fingerprint

Toll-Like Receptor 4
Interleukin-8
Phospholipids
Toll-Like Receptors
Toll-Like Receptor 1
Toll-Like Receptor 2
Endothelial Cells
HEK293 Cells
Lipids
Toll-Like Receptor 6
Atherosclerosis
Atherectomy
Rhodobacter sphaeroides
Atherosclerotic Plaques
Transfection
1-palmitoyl-2-arachidonyl-3-phosphorylcholine
Arteries
Gene Expression

Keywords

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

Cite this

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Toll-like receptor 4 signalling is neither sufficient nor required for oxidised phospholipids mediated induction of interleukin-8 expression. / Erridge, C.; Webb, D.J.; Spickett, C.M.

In: Atherosclerosis, Vol. 193, No. 1, 2007, p. 77-85.

Research output: Contribution to journalArticle

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