Gene interactions and pathways from curated databases and text-mining
Acta Biochim Biophys Sin (Shanghai) 2011, PMID: 22015781

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

Yu, Miao; Kang, Xiaomin; Xue, Hong; Yin, Hongchao

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 efflux mediator ABCA1, which resulted from the activation of TLR4 by ligands. 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 efflux.

Diseases/Pathways annotated by Medline MESH: Atherosclerosis
Document information provided by NCBI PubMed

Text Mining Data

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

TLR4 ⊣ mTOR: " The mTOR inhibitor rapamycin blocked mTOR phosphorylation and inhibited TLR4 expression induced by ox-LDL "

TLR4 → ox-LDL: " The mTOR inhibitor rapamycin blocked mTOR phosphorylation and inhibited TLR4 expression induced by ox-LDL "

TLR4 ⊣ raptor: " Silencing mTOR, rictor or raptor protein expression by small interfering RNA, also inhibited the up-regulation of TLR4 expression, respectively "

TLR4 → mTOR: " Inhibition of ox-LDL induced mTOR activation reduced TLR4 expression, and improved the impaired lipid efflux "

TLR4 → ox-LDL: " Inhibition of ox-LDL induced mTOR activation reduced TLR4 expression, and improved the impaired lipid efflux "

mTOR → ox-LDL: " Inhibition of ox-LDL induced mTOR activation reduced TLR4 expression, and improved the impaired lipid efflux "

Manually curated Databases

No curated data.