Different patterns of IL-1 beta secretion, adhesion molecule expression and apoptosis induction in human endothelial cells treated with 7 alpha-, 7 beta-hydroxycholesterol, or 7-ketocholesterol

Among oxysterols oxidized at C7 (7 alpha-, 7 beta-hydrosycholesterol, and 7 -ketocholesterol), 7 beta-hydrosycholesterol and 7-ketocholesterol involved in the cytotoxicity of oxidized low density lipoproteins (LDL) are potent inducers of apoptosis, Here, we asked whether all oxysterols oxidized at C7 were able to trigger apoptosis, to stimulate interleukin (IL)-1 beta and/o r tumor necrosis factor (TNF)-alpha secretion, and to enhance adhesion mole cule expression (intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin) on human umbilical venous end othelial cells (HUVECs), Only 7 beta-hydroxycholesterol and 7-ketocholester ol were potent inducers of apoptosis and of IL-IP secretion, TNF-alpha secr etion was never detected. Depending on the oxysterol considered, various le vels of ICAM-1, VCAM-1 and E-selectin expression were observed. So, oxyster ols oxidized at C7 differently injure and activate HUVECs, and the alpha- o r beta-hydroxyl radical position plays a key role in apoptosis and IL-1 bet a secretion. (C) 1998 Federation of European Biochemical Societies.