25-hydroxycholesterol, 7b-hydroxycholesterol and 7-ketocholesterol upregulate interleukin-8 expression independently of toll-like receptor 1, 2, 4 or 6 signalling in human macrophages

Clett Erridge, David J. Webb, C.M. Spickett

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Recent studies have shown that Toll-like receptor (TLR)- signalling contributes significantly to the inflammatory events of atherosclerosis. As products of cholesterol oxidation (oxysterols) accumulate within atherosclerotic plaque and have been proposed to contribute to inflammatory signalling in the diseased artery, we investigated the potential of 7-ketocholesterol (7-KC), 7β-hydroxycholesterol (7β-HC) and 25-hydroxycholesterol (25-HC) to stimulate inflammatory signalling via the lipid-recognising TLRs 1, 2, 4 and 6. Each oxysterol stimulated secretion of the inflammatory chemokine interleukin-8 (IL-8), but not IκB degradation or tumour necrosis factor- release from monocytic THP-1 cells. Transfection of TLR-deficient HEK-293 cells with TLRs 1, 2, 4 or 6 did not increase sensitivity to the tested oxysterols. Moreover, blockade of TLR2 or TLR4 with specific inhibitors did not reduce 25-hydroxycholesterol (25-HC) induced IL-8 release from THP-1 cells. We conclude that although the oxysterols examined in this study may contribute to increased expression of certain inflammatory genes, this occurs by mechanisms independent of TLR signalling.
LanguageEnglish
Pages260-266
Number of pages6
JournalFree Radical Research
Volume41
Issue number3
DOIs
Publication statusPublished - 2007

Fingerprint

Toll-Like Receptor 1
Hydroxycholesterols
Toll-Like Receptor 2
Macrophages
Interleukin-8
Toll-Like Receptors
Up-Regulation
HEK293 Cells
Atherosclerotic Plaques
Chemokines
Transfection
Atherosclerosis
Arteries
Tumor Necrosis Factor-alpha
Genes
Cholesterol
Lipids
Degradation
Oxidation
7-ketocholesterol

Keywords

  • oxysterols
  • inflammation
  • atherosclerosis
  • Toll-like receptors

Cite this

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abstract = "Recent studies have shown that Toll-like receptor (TLR)- signalling contributes significantly to the inflammatory events of atherosclerosis. As products of cholesterol oxidation (oxysterols) accumulate within atherosclerotic plaque and have been proposed to contribute to inflammatory signalling in the diseased artery, we investigated the potential of 7-ketocholesterol (7-KC), 7β-hydroxycholesterol (7β-HC) and 25-hydroxycholesterol (25-HC) to stimulate inflammatory signalling via the lipid-recognising TLRs 1, 2, 4 and 6. Each oxysterol stimulated secretion of the inflammatory chemokine interleukin-8 (IL-8), but not IκB degradation or tumour necrosis factor- release from monocytic THP-1 cells. Transfection of TLR-deficient HEK-293 cells with TLRs 1, 2, 4 or 6 did not increase sensitivity to the tested oxysterols. Moreover, blockade of TLR2 or TLR4 with specific inhibitors did not reduce 25-hydroxycholesterol (25-HC) induced IL-8 release from THP-1 cells. We conclude that although the oxysterols examined in this study may contribute to increased expression of certain inflammatory genes, this occurs by mechanisms independent of TLR signalling.",
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25-hydroxycholesterol, 7b-hydroxycholesterol and 7-ketocholesterol upregulate interleukin-8 expression independently of toll-like receptor 1, 2, 4 or 6 signalling in human macrophages. / Erridge, Clett; Webb, David J.; Spickett, C.M.

In: Free Radical Research, Vol. 41, No. 3, 2007, p. 260-266.

Research output: Contribution to journalArticle

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