Journal
FEBS LETTERS
Volume 579, Issue 7, Pages 1707-1714Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2005.01.076
Keywords
lipopolysaccharide; cyclodextrin; tumor necrosis factor; CD14; lipid raft; macrophage
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The potential use of a-cyclodextrin and its hydrophilic a-cyclodextrin derivatives (alpha-CyDs) as antagonists against lipopolysaccharide (LPS), which stimulates the nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production as well as nuclear factor-kappa B (NF-kappa B) activation in macrophages was examined. Of three alpha-CyDs used in the present study, 2,6-di-O-methyl-alpha-CyD (DM-alpha-CyD) had greater inhibitory activity than did the other CyDs against NO and TNF-alpha production through an impairment of gene expression in macrophage cell lines and primary macrophages stimulated with LPS and lipid A in a concentration-dependent manner. Concomitantly, DM-alpha-CyD inhibited NF-kappa B translocation into nucleus. These inhibitory effects of DM-alpha-CyD could be attributed to the release of CD14 from lipid rafts caused by an efflux of phospholipids, but not cholesterol. These results suggest that DM-alpha-CyD may have promise as a potent and unique antagonist for excess activation of macrophages stimulated with LPS. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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