Effect of T0901317 on hepatic proinflammatory gene expression in apoE-/- mice fed a high-fat/high-cholesterol diet

Objective. In present study, we employed cDNA-based microarray technique to investigate the effect of a synthetic LXR ligand T0901317 on hepatic gene expression of proinflammatory cytokines in apolipoprotein E knockout mice fed an atherogenic diet. Methods and results. Male 8-week-old apoE-/- mice were randomly divided into four groups, baseline group, vehicle group, prevention group and treatment group. All of the mice were fed a high-fat/high-cholesterol diet with or without LXR agonist T0901317 for 8 or 14 weeks. Gene array analysis found 17 atherosclerosis-related genes with a 2- to 8-fold difference in expression level between vehicle-treated group and T0901317-treated group. It induced mRNA expression of proinflammatory cytokine tumor necrosis factor (TNF), but inhibited gene expression of several other proinflammatory cytokines including interleukin (IL)-1 alpha, IL-6, and IL-7 in the liver. C-reactive protein, TNF, matrix metalloproteinase-9, IL-1 alpha, IL-6, and IL-7 were verified by real-time quantitative PCR. Next, enzyme-linked immunosorbent assay analyses showed up-regulation of TNF alpha levels and down-regulation of IL-alpha, IL-6, IL-7 levels in plasma sample. Conclusion. The synthetic LXR agonist T0901317 has paradoxical roles in hepatic gene expression of proinflammatory cytokines in apoE-/- mice.