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

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Title
Inhibition of cytokine-induced IκB kinase activation as a mechanism contributing to the anti-atherogenic activity of tilianin in hyperlipidemic mice
Author(s)
K W Nam; J Kim; Jung Joo Hong; J H Choi; W Mar; M H Cho; Y M Kim; Sei Ryang Oh; Hyeong Kyu Lee; Ki Hoan Nam; G T Oh
Bibliographic Citation
Atherosclerosis, vol. 180, no. 1, pp. 27-35
Publication Year
2005
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.
Keyword
AtherosclerosisCytokineIKKTilianin
ISSN
0021-9150
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.atherosclerosis.2004.11.022
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > National Primate Research Center > 1. Journal Articles
Ochang Branch Institute > 1. Journal Articles
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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