RRC ID 19352
著者 Iftakhar-E-Khuda I, Koide N, Hassan F, Noman AS, Dagvadorj J, Tumurkhuu G, Naiki Y, Komatsu T, Yoshida T, Yokochi T.
タイトル Novel mechanism of U18666A-induced tumour necrosis factor-alpha production in RAW 264.7 macrophage cells.
ジャーナル Clin Exp Immunol
Abstract U18666A is a cholesterol transport-inhibiting agent that is used widely to mimic Niemann-Pick type C disease. The effect of U18666A on tumour necrosis factor (TNF)-alpha production in mouse macrophage cell line, RAW 264.7 cells and peritoneal macrophages was examined. U18666A induced TNF-alpha mRNA expression 48 h after the treatment, and TNF-alpha production 48 and 72 h after stimulation in RAW 264.7 cells. U18666A accumulated intracellular free cholesterol in the culture of normal medium but not cholesterol-free medium. U18666A also induced reactive oxygen species (ROS) generation in normal medium but much less in cholesterol-free medium. Anti-oxidant N-acetyl-L-cysteine (NAC) abolished U18666A-induced TNF-alpha production. U18666A led to the phosphorylation of p38 mitogen-activated protein kinase 24 and 48 h after the stimulation and the p38 activation was inhibited in presence of cholesterol-free medium or NAC. A p38 inhibitor reduced U18666A-induced TNF-alpha production. Taken together, U18666A was suggested to induce TNF-alpha production in RAW 264.7 cells via free cholesterol accumulation-mediated ROS generation.
巻・号 155(3)
ページ 552-8
公開日 2009-3-1
DOI 10.1111/j.1365-2249.2008.03779.x
PII CEI3779
PMID 19220841
PMC PMC2669532
MeSH Androstenes / pharmacology* Animals Anticholesteremic Agents / pharmacology* Cell Line Cholesterol / metabolism Enzyme Activation Macrophages / drug effects Macrophages / metabolism* Mice Niemann-Pick Diseases / immunology Reactive Oxygen Species / metabolism Tumor Necrosis Factor-alpha / biosynthesis* p38 Mitogen-Activated Protein Kinases / metabolism
IF 3.532
引用数 5
WOS 分野 IMMUNOLOGY
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)