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

Cited 26 time in Web of Science Cited 27 time in Scopus
Authors
Nam, Kung-Woo; Kim, Jihyun; Hong, Jung-Joo; Choi, Jae-Hoon; Mar, Woonchon; Cho, Myung-Haing; Kim, Young-Myeong; Oh, Sei-Ryang; Lee, Hyeong-Kyu; Nam, Ki-Hoan; Oh, Goo Taeg
Issue Date
2005-05
Citation
Atherosclerosis, Vol.180 No.1, pp.27-35
Keywords
tilianinatherosclerosisIKKcytokine
Abstract
Tilianin has been shown to down-regulate TNF-alpha 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-alpha and IL-1 beta, 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-alpha andIL-1 beta mRNA in response to treatment with lipopolysaccharide; these increases were inhibited by co-treatment with tilianin. Moreover, tilianin inhibited NF-kappa B activation, as determined by electrophoretic mobility shift and NF-kappa B promoter assays. Upstream of NF-kappa B activation, tilianin inhibited I kappa B kinase activation and the subsequent phosphorylation and degradation of I kappa B alpha protein. These results suggest that tilianin ameliorates atherosclerosis by inhibiting the production of the NF-kappa B-dependent pro-inflammatory cytokines, TNF-alpha and IL-1 beta, via the inhibition of I kappa B kinase activity. (c) 2004 Elsevier Ireland Ltd. All rights reserved.
ISSN
0021-9150
URI
https://hdl.handle.net/10371/172317
DOI
https://doi.org/10.1016/j.atherosclerosis.2004.11.022
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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