Inhibition of cytokine-induced IκB kinase activation as a mechanism contributing to the anti-atherogenic activity of tilianin in hyperlipidemic mice

Kung Woo Nam, Jiyun Kim, Jung Joo Hong, Jae Hoon Choi, Woonchon Mar, Myung Haing Cho, Young Myeong Kim, Sei Ryang Oh, Hyeong Kyu Lee, Ki Hoan Nam, Goo Taeg Oh

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Tilianin has been shown to down-regulate TNF-α induced expression of vascular cell adhesion molecules in endothelial cells. In this study, we examined the anti-atherogenic effects and molecular mechanism of tilianin in vitro and in vivo. Male low-density lipoprotein receptor null mice (Ldlr-/-) fed a high cholesterol diet showed significant increases in the size of atherosclerotic lesions, as well as increased plasma levels of total cholesterol, triglycerides, and the pro-inflammatory cytokines TNF-α and IL-1β, when compared with Ldlr-/- mice fed a normal diet. Mice fed the high cholesterol diet supplemented with tilianin showed significantly reduced lesion sizes and reductions in cytokine levels, without significant changes in serum cholesterol levels. Primary cultured peritoneal macrophages from Ldlr-/- mice showed increased level of TNF-α andIL-1β mRNA in response to treatment with lipopolysaccharide; these increases were inhibited by co-treatment with tilianin. Moreover, tilianin inhibited NF-κB activation, as determined by electrophoretic mobility shift and NF-κB promoter assays. Upstream of NF-κB activation, tilianin inhibited IκB kinase activation and the subsequent phosphorylation and degradation of IκBα protein. These results suggest that tilianin ameliorates atherosclerosis by inhibiting the production of the NF-κB-dependent pro-inflammatory cytokines, TNF-α and IL-1β, via the inhibition of IκB kinase activity.

Original languageEnglish
Pages (from-to)27-35
Number of pages9
JournalAtherosclerosis
Volume180
Issue number1
DOIs
StatePublished - May 2005

Keywords

  • Atherosclerosis
  • Cytokine
  • IKK
  • Tilianin

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