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.


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)-1alpha, IL-6, and IL-7 in the liver. C-reactive protein, TNF, matrix metalloproteinase-9, IL-1alpha, IL-6, and IL-7 were verified by real-time quantitative PCR. Next, enzyme-linked immunosorbent assay analyses showed up-regulation of TNFalpha levels and down-regulation of IL-alpha, IL-6, IL-7 levels in plasma sample.


CONCLUSIONS
The synthetic LXR agonist T0901317 has paradoxical roles in hepatic gene expression of proinflammatory cytokines in apoE-/- mice.
Dai
Xiaoyan
X
Institute of Cardiovascular Research, Nanhua University, Hengyang, Hunan 421001, China.
Ou
Xiang
X
Hao
Xinrui
X
Cao
Dongli
D
Tang
Yaling
Y
Hu
Yanwei
Y
Li
Xiaoxu
X
Tang
Chaoke
C
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D002097:C-Reactive Protein / Q000235:genetics; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000819:agonists; D015870:Gene Expression / Q000276:immunology; D020869:Gene Expression Profiling; D006845:Hydrocarbons, Fluorinated; D053582:Interleukin-1alpha / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D015851:Interleukin-7 / Q000097:blood / Q000235:genetics; D008099:Liver / Q000276:immunology*; D000071518:Liver X Receptors; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D020411:Oligonucleotide Array Sequence Analysis; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D001057:Apolipoproteins E; D002097:C-Reactive Protein; D002791:Cholesterol, Dietary; D004268:DNA-Binding Proteins; D006845:Hydrocarbons, Fluorinated; D053582:Interleukin-1alpha; D015850:Interleukin-6; D015851:Interleukin-7; D000071518:Liver X Receptors; D020780:Matrix Metalloproteinase 9; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides