首页|Toll-like receptor 4 is up-regulated by mTOR activation during THP-1 macrophage foam cells formation

Toll-like receptor 4 is up-regulated by mTOR activation during THP-1 macrophage foam cells formation

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Macrophage foam cells formation is the most important process in atherosclerotic plaque formation and development.Toll-like receptor 4 (TLR4) is one of the important innate immune sensors of endogenous damage signals and crucial for regulating inflammation.Growing evidence indicates that TLR4 plays a very important role in macrophage foam cells formation.However,the underlying mechanisms regulating TLR4 expression in macrophage are not fully understood.In this study,we induced THP-1 macrophage foam cells formation with oxidative modified low-density lipoprotein (ox-LDL).We observed that TLR4 mRNA and protein expression were markedly up-regulated,and the phosphorylation of mammalian target of rapamycin (mTOR) and its downstream target p70S6K were promoted during foam cells formation.The mTOR inhibitor rapamycin blocked mTOR phosphorylation and inhibited TLR4 expression induced by ox-LDL.Silencing mTOR,rictor or raptor protein expression by small interfering RNA,also inhibited the up-regulation of TLR4 expression,respectively.Inhibition of mTOR with rapamycin reversed the down-regulation of cellular lipid effiux mediator ABCA1,which resulted from the activation of TLR4 by iigands.These data suggested that TRL4 expression was up-regulated by a mechanism dependent on mTOR signal pathway activation during THP-1 macrophage foam cells formation.Inhibition of ox-LDL induced mTOR activation reduced TLR4 expression,and improved the impaired lipid effiux.

foam cellsmacrophagetoll-like receptor 4atherosclerosis

Miao Yu、Xiaomin Kang、Hong Xue、Hongchao Yin

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Key laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China

Department of Pathology, Institute of Basic Medical Sciences, School of Basic Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China

Department of Pathology, Institute of Basic Medical Sciences, School of Basic Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China <英作者单位五>=Department of Pathology, Institute of Basic Medical Sciences, School of Basic Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China

国家自然科学基金Natural Science Foundation of Beijing

305707207083113

2011

10.1093/abbs/gmr093

生物化学与生物物理学报(英文版)
中国科学院上海生物化学研究所

生物化学与生物物理学报(英文版)

CSTPCDCSCDSCI
影响因子：0.772
ISSN：1672-9145
年,卷(期)：2011.43(12)
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