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Updated: Jul 25, 2026

Determination of Tolerable Fatty Acids and Cholera Toxin Concentrations Using Human Intestinal Epithelial Cells and BALB/c Mouse Macrophages
Published on: May 30, 2013
25-hydroxycholesterol induces lipopolysaccharide-tolerance and decreases a lipopolysaccharide-induced TNF-alpha
M C Englund1, A L Karlsson, O Wiklund
1The Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, Göteborg University, SE-413 45 Göteborg, Sweden. mikael.englund@wlab.wall.gu.se
Abstract:
Several different oxysterols are formed when LDL is oxidized. The role of oxysterols in the inflammatory process in the atherosclerotic plaque is not totally elucidated. In this study we have investigated the effect of four different oxysterols on an LPS-induced TNF-alpha secretion in human macrophages. Cultured human macrophages were incubated with 7-keto-, 7beta-hydroxy-, 27-hydroxy- and 25-hydroxycholesterol for 24 h before exposure to endotoxin (LPS) for 3 h. All oxysterols, except 7-ketocholesterol, significantly decreased an LPS-induced TNF-alpha secretion. The most pronounced effect was obtained with 25-hydroxycholesterol, where the TNF-alpha secretion was reduced to 8%. This decreased effect was also found on the TNF-alpha mRNA level. The decreased LPS-induced TNF-alpha secretion coincided with an increased binding of the transcription factors Sp1 and Sp3 to the TNF-alpha promoter. In vitro studies of the TNF-alpha promoter suggests possible interactions between Sp1 and Sp3 and the NF-kappaB transcription factor complex that might affect the transcriptional initiation.
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