Macrophages Isolated From Human Atherosclerotic Plaques Produce IL-8, and Oxysterols May Have a Regulatory Function for IL-8 Production

Abstract

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.

Marked accumulation of 27-hydroxycholesterol in SPG5 patients with hereditary spastic paresis

“…Under in vivo conditions, the oxysterols are always present together with a very high excess of cholesterol, and this cholesterol may decrease or prevent the activity of the oxysterol ( 31 ). It has been reported that 25-hydroxycholesterol induces production of interleukin 1 ␤ and interleukin 8 from human macrophages ( 32,33 ). It cannot be excluded that a local interleukin release as a consequence of the high levels of 25-hydroxycholesterol may be of pathogenetic importance in the SPG5 patients.…”

Modulation by Insulin of the Co-Localized LDL Receptor in Normal and Type-I Diabetic Subjects

“…Retention of lipoproteins [25,26] in the arterial wall initiates the early stage of atherosclerosis. This is then followed by activation of endothelial expression of adhesion molecules [27][28][29], development of cholesterol-laden foam cells [30,31] and formation of atherosclerotic plaque [32][33][34]. The gly- cated lipoprotein(s) affects LDL receptor activity.…”

High-density lipoprotein protects macrophages from oxidized low-density lipoprotein-induced apoptosis by promoting efflux of 7-ketocholesterol via ABCG1

“…Cellular accumulation of 7-ketocholesterol leads to increased production of reactive oxygen species and induces apoptosis in various cell types, including macrophages, endothelial cells, and smooth muscle cells (12)(13)(14)(15). In addition, oxysterols induce inflammatory gene expression in monocytemacrophages (34)(35)(36)(37). Therefore, 7-ketocholesterol and related oxysterols probably have an important role in the pathogenesis of atherosclerosis.…”