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Effect of T0901317 on Hepatic Proinflammatory Gene Expression in ApoE−/− Mice Fed a High-fat/high-cholesterol Diet

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Abstract

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

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Abbreviations

LXR:

liver X receptor

apoE−/−:

apolipoprotein E knockout

TNF:

tumor necrosis factor

IL:

interleukin

MMP:

matrix metalloproteinase

CRP:

C-reactive protein

ELISA:

enzyme-linked immunosorbent assay

TG:

triglyceride

TC:

total cholesterol

HDL-C:

high density lipoprotein cholesterol

Apo:

apolipoprotein

INOS:

inducible nitric oxide synthase

COX2:

cyclooxygenase 2

LPS:

lipopolysaccharide

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

ABC:

ATP-binding cassette transporter

ECM:

extracellular matrix

22(R)-HC:

22(R)-hydroxycholesterol

9cRA:

9-cis-retinoic acid

GR:

glucocorticoid receptor

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Acknowledgment

The authors gratefully acknowledge the financial support from the National Natural Sciences Foundation of China (30470720), Post-doctor Sciences Foundation of China (2005037157), and Hunan Provincial Natural Sciences Foundation of China (06jj5058).

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Authors and Affiliations

  1. Institute of Cardiovascular Research, Nanhua University, Hengyang, Hunan, 421001, China

    Xiaoyan Dai, Xiang Ou, Xinrui Hao, Dongli Cao, Yaling Tang, Yanwei Hu, Xiaoxu Li & Chaoke Tang

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  1. Xiaoyan Dai
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Correspondence to Chaoke Tang.

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Dai, X., Ou, X., Hao, X. et al. Effect of T0901317 on Hepatic Proinflammatory Gene Expression in ApoE−/− Mice Fed a High-fat/high-cholesterol Diet. Inflammation 30, 105–117 (2007). https://doi.org/10.1007/s10753-007-9026-2

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