24S-hydroxycholesterol induces inflammatory gene expression in primary human neural cells

Abstract

24S-hydroxycholesterol, the primary oxidation product of cholesterol in the brain, plays a key role in cholesterol elimination and homeostasis. While the concentration of this neurotoxic oxysterol decreases with age, 24S-hydroxycholesterol is elevated in Alzheimer's disease. In this study, we examined the effects of 24S-hydroxycholesterol on gene expression in human neural cells, a primary coculture of neurons and glia useful for studying pathogenic mechanisms in Alzheimer's disease. DNA array and Western analysis revealed elevations in the expression of a pro-inflammatory gene family that included beta-amyloid precursor protein, cyclooxygenase-2, cytosolic phospholipase A2 and heat shock protein 70, an effect that was partially suppressed by simvastatin. These data indicate that cholesterol oxides induce atypical gene expression in neural cells that may contribute to the etiology or pathogenesis of inflammatory brain disease.