TY - JOUR
T1 - Novel mechanism of U18666A-induced tumour necrosis factor-α production in RAW 264.7 macrophage cells
AU - Iftakhar-E-Khuda, I.
AU - Koide, N.
AU - Hassan, F.
AU - Noman, A. S.M.
AU - Dagvadorj, J.
AU - Tumurkhuu, G.
AU - Naiki, Y.
AU - Komatsu, T.
AU - Yoshida, T.
AU - Yokochi, T.
PY - 2009/3
Y1 - 2009/3
N2 - 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)-α production in mouse macrophage cell line, RAW 264.7 cells and peritoneal macrophages was examined. U18666A induced TNF-α mRNA expression 48 h after the treatment, and TNF-α 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-α 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-α production. Taken together, U18666A was suggested to induce TNF-α production in RAW 264.7 cells via free cholesterol accumulation-mediated ROS generation.
AB - 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)-α production in mouse macrophage cell line, RAW 264.7 cells and peritoneal macrophages was examined. U18666A induced TNF-α mRNA expression 48 h after the treatment, and TNF-α 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-α 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-α production. Taken together, U18666A was suggested to induce TNF-α production in RAW 264.7 cells via free cholesterol accumulation-mediated ROS generation.
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U2 - 10.1111/j.1365-2249.2008.03779.x
DO - 10.1111/j.1365-2249.2008.03779.x
M3 - Article
C2 - 19220841
AN - SCOPUS:59249105557
SN - 0009-9104
VL - 155
SP - 552
EP - 558
JO - Clinical and Experimental Immunology
JF - Clinical and Experimental Immunology
IS - 3
ER -