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Effects of Resveratrol on the Expression and DNA Methylation of Cytokine Genes in Diabetic Rat Aortas

  • Xu-dan Lou
  • Hai-dong WangEmail author
  • Shi-jin Xia
  • Sven Skog
  • Jiao Sun
Original Article

Abstract

This paper studies the expression of proinflammatory cytokines such as IL-1β, IL-6, TNF-α, and IFN-γ and anti-inflammatory cytokines such as IL-10 in diabetic rat aortas, the effects of resveratrol on these cytokines, and the potential epigenetic mechanisms involved. The experiment was performed on rats divided into four groups: normal group (NC), normal interventional group (NB), diabetic group (DM), and diabetic interventional group (DB). The NB and DB groups were treated with resveratrol. After more than 3 months, the rats’ aortas were removed and analyzed for cytokines by using immunohistochemistry, Western blotting, real-time PCR, and methylation-specific PCR. Histological localization of these cytokines was mainly found in the arterial intima of diabetic rats. The protein and mRNA expression levels of IL-1β, IL-6, TNF-α, and IFN-γ were significantly higher in the DM group than in the NC group (p < 0.05), whereas in the resveratrol-treated groups (NB and DB), the levels were relatively lower than those in the corresponding groups. The DM group showed reduced levels of DNA methylation at the specific cytosine phosphate guanosine sites of IL-1β, IL-6, TNF-α, and IFN-γ, relative to those in the NC group (p < 0.01), and these levels were increased by resveratrol. In contrast, IL-10 was dramatically methylated and showed decreased expression in response to high glucose, and resveratrol reversed this effect. These results demonstrate that the inflammatory response is involved in diabetic macroangiopathy. Resveratrol inhibits the expression of proinflammatory cytokines and thus may have a protective effect on the aorta in hyperglycemia. Thus, DNA methylation, an epigenetic gene silencing signal, may be responsible for these two phenomena.

Keywords

Inflammatory cytokines Resveratrol DNA methylation 

Notes

Acknowledgments

This study was supported by Shanghai Committee of Science and Technology Development Funds for Basic Research under Grant No. 10JC1404800 and the National Natural Science Foundation of China under Grant No. 31171129.

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Copyright information

© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2014

Authors and Affiliations

  • Xu-dan Lou
    • 1
  • Hai-dong Wang
    • 1
    • 2
    Email author
  • Shi-jin Xia
    • 3
    • 4
  • Sven Skog
    • 5
  • Jiao Sun
    • 1
  1. 1.Endocrinology Department, Huadong HospitalFudan UniversityShanghaiChina
  2. 2.Diabetes Association of Administration and EducationShanghaiChina
  3. 3.Shanghai Institute of GeriatricsHuadong Hospital, Fudan UniversityShanghaiChina
  4. 4.Institute of Respiratory Diseases, Xinqiao HospitalThird Military Medical UniversityChongqingChina
  5. 5.Sino-Swed Molecular Bio-Medicine Research InstituteShenzhenChina

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