Induction of apoptosis and of interleukin‐1β secretion by 7β‐hydroxycholesterol and 7‐ketocholesterol: partial inhibition by Bcl‐2 overexpression

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Abstract
The oxysterols, 7β-hydroxycholesterol and 7-ketocholesterol, are involved in the cytotoxicity of oxidized LDL. To elucidate their molecular mechanisms, the human promonocytic leukemia cells U937 and U4 were used. U4 cells overexpressing Bcl-2 were obtained by transfection of U937 cells. 7β-hydroxycholesterol and 7-ketocholesterol induced nuclear condensation and/or fragmentation, internucleosomal DNA fragmentation, and IL-1β secretion, which were partially inhibited by Bcl-2 overexpression. These findings underline that these oxysterols could constitute major risk factors in atherosclerosis by their cytotoxicity and their ability to induce IL-1β release which might favor the recruitment of immunocompetent cells in the atherosclerotic plaque.