TNF-alpha stimulates the ACAT1 expression in differentiating monocytes to promote the CE-laden cell formation

	TNF-alpha stimulates the ACAT1 expression in differentiating monocytes to promote the CE-laden cell formation
	Lei, L; Xiong, Y; Chen, J; Yang, JB; Wang, Y; Yang, XY; Chang, CCY; Song, BL; Chang, TY; Li, BL
刊名	JOURNAL OF LIPID RESEARCH
	2009
卷号	50 期号:6 页码:1057-1067
关键词	atherosclerosis cholesterol esterification inflammatory cytokine lipid metabolism transcription control
通讯作者	Li, BL (reprint author), Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.,blli@sibs.ac.cn
英文摘要	High levels of the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) are present in atherosclerotic lesions. TNF-alpha regulates expression of multiple genes involved in various stages of atherosclerosis, and it exhibits proatherosclerotic and antiatherosclerotic properties. ACAT catalyzes the formation of cholesteryl esters (CE) in monocytes/macrophages, and it promotes the foam cell formation at the early stage of atherosclerosis. We hypothesize that TNF-alpha may be involved in regulating the ACAT gene expression in monocytes/macrophages. In this article, we show that in cultured, differentiating human monocytes, TNF-alpha enhances the expression of the ACAT1 but not ACAT2 gene, increases the cholesteryl ester accumulation, and promotes the lipid-laden cell formation. Several other proinflammatory cytokines tested do not affect the ACAT1 gene expression. The stimulation effect is consistent with a receptor-dependent process, and is blocked by using nuclear factor-kappa B (NF-kappa B) inhibitors. A functional and unique NF-kappa B element located within the human ACAT1 gene proximal promoter is required to mediate the action of TNF-alpha. Our data demonstrate that TNF-alpha, through the NF-kappa B pathway, specifically enhances the expression of human ACAT1 gene to promote the CE-laden cell formation from the differentiating monocytes, and our data support the hypothesis that TNF-alpha is proatherosclerotic during early phase of lesion development.-Lei, L., Y. Xiong, J. Chen, J-B. Yang, Y. Wang, X-Y. Yang, C. C. Y. Chang, B-L. Song, T-Y. Chang, and B-L. Li. TNF-alpha stimulates the ACAT1 expression in differentiating monocytes to promote the CE-laden cell formation. J. Lipid Res. 2009. 50: 1057-1067.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	TUMOR-NECROSIS-FACTOR ; A-CHOLESTEROL ACYLTRANSFERASE-1 ; NF-KAPPA-B ; ACYL-COENZYME ; GENE-EXPRESSION ; SIGNAL-TRANSDUCTION ; HUMAN MACROPHAGES ; RETINOIC ACID ; IN-VITRO ; ATHEROSCLEROSIS
收录类别	SCI
语种	英语
WOS记录号	WOS:000266114500004
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1210]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Lei, L,Xiong, Y,Chen, J,et al. TNF-alpha stimulates the ACAT1 expression in differentiating monocytes to promote the CE-laden cell formation[J]. JOURNAL OF LIPID RESEARCH,2009,50(6):1057-1067.
APA	Lei, L.,Xiong, Y.,Chen, J.,Yang, JB.,Wang, Y.,...&Li, BL.(2009).TNF-alpha stimulates the ACAT1 expression in differentiating monocytes to promote the CE-laden cell formation.JOURNAL OF LIPID RESEARCH,50(6),1057-1067.
MLA	Lei, L,et al."TNF-alpha stimulates the ACAT1 expression in differentiating monocytes to promote the CE-laden cell formation".JOURNAL OF LIPID RESEARCH 50.6(2009):1057-1067.