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Involvement of CD14 in the inhibitory effects of dimethyl‐α‐cyclodextrin on lipopolysaccharide signaling in macrophages
Author(s) -
Motoyama Keiichi,
Arima Hidetoshi,
Nishimoto Yoji,
Miyake Kensuke,
Hirayama Fumitoshi,
Uekama Kaneto
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.01.076
Subject(s) - lipopolysaccharide , chemistry , nitric oxide , cd14 , lipid a , tumor necrosis factor alpha , macrophage , cyclodextrin , tlr4 , pharmacology , efflux , biochemistry , in vitro , signal transduction , receptor , biology , endocrinology , organic chemistry
The potential use of α‐cyclodextrin and its hydrophilic α‐cyclodextrin derivatives (α‐CyDs) as antagonists against lipopolysaccharide (LPS), which stimulates the nitric oxide (NO) and tumor necrosis factor‐α (TNF‐α) production as well as nuclear factor‐κB (NF‐κB) activation in macrophages was examined. Of three α‐CyDs used in the present study, 2,6‐di‐ O ‐methyl‐α‐CyD (DM‐α‐CyD) had greater inhibitory activity than did the other CyDs against NO and TNF‐α 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‐α‐CyD inhibited NF‐κB translocation into nucleus. These inhibitory effects of DM‐α‐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‐α‐CyD may have promise as a potent and unique antagonist for excess activation of macrophages stimulated with LPS.