Macrophages isolated from human atherosclerotic plaques produce IL-8, and oxysterols may have a regulatory function for IL-8 production.
Oxysterols are biologically active molecules generated during oxidation of LDL. Several of these oxysterols were found in macrophage-derived foam cells from human atherosclerotic tissue (eg, 7-hydroxycholesterol, 7-ketocholesterol, 5-epoxycholesterol, and 25-hydroxycholesterol). A specific stimulation of interleukin-8 (IL-8) production by oxidized LDL (oxLDL) has been shown by other investigators. In foam cells from human atherosclerotic tissue, we found high levels of IL-8 (183.1 pg/10(6) cells) compared with monocytes (23.2 pg/10(6) cells) or monocyte-derived macrophages in culture (1.5 pg/10(6) cells). When monocytes and monocyte-derived macrophages, in vitro, were exposed to a series of different oxysterols, we found that all oxysterols tested had a tendency to stimulate IL-8 production but that 25-hydroxycholesterol was the most potent one. This stimulation of IL-8 production was time and dose dependent and could be blocked by cycloheximide. These results indicate that oxysterols in oxLDL may have a regulatory effect on IL-8 production. IL-8, a potent chemoattractant, may play a role in the recruitment of T lymphocytes and smooth muscle cells into the subendothelial space and may contribute to the formation of atherosclerotic lesions.
Liu
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Wallenberg Laboratory for Cardiovascular Research, Göteborg University, Sweden.
Hultén
L M
LM
Wiklund
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D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D013261:Sterols / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D006888:Hydroxycholesterols; D007375:Interleukin-1; D016209:Interleukin-8; D013261:Sterols; D014409:Tumor Necrosis Factor-alpha; C007997:25-hydroxycholesterol