Lipopolysaccharide Down-regulates ABCA1 Expression in Foam Cells in a Nucleus Factor-κB Pathway-dependent Manner*

Abstract

The immnue-inflammatory response mediated by LPS is firmly related to the development of atherosclerosis. ABCA1 has been identified to play a key role in the cellular cholesterol efflux which is regarded to anti-atherosclerosis. To investigate the changes of cholesterol efflux, ATP-binding cassette transporter A1 (ABCA1) mRNA and protein expression in THP-1 macrophage derived foam cells treated with LPS, and to discover the role of TLR4/NF-κB pathway and LXRs in this process. The foam cells were exposed to different concentration of LPS for 24 h or exposed to LPS for different times, and more, the cells were treated with LPS along or together with N-p-Tosyl-L-phenylalanine chloromethyl ketone (TPCK) for 24 h. The mRNA levels of ABCA1, TLR4 and LXRα were measured by reverse transcriptase-polymerase chain reaction,and the protein levels of ABCA1, LXRα and intranuclear NF-κB p65 were measured by Western blotting. Cellular lipid accumulation was determined by high performance liquid chromatography analysis. Cholesterol efflux was determined by FJ-2107P type liquid scintillator. The results show that the expression of ABCA1 were decreased in a dose- and time-dependent manner after treated with LPS, while TLR4 expression and the intranuclear NF-κB p65 protein level were increased by LPS, and these changes can be reversed partly by pretreatment with TPCK. LPS and TPCK can not effect LXRα expression. The results also show that cellular lipid accumulation was increased, while the cellular cholesterol efflux was decreased in THP-1 macrophage derived foam cells after exposured to LPS for 24 h. It was concluded that LPS can down-regulate the expression of ABCA1, promote the accumulation of lipid and decrease cellular cholesterol efflux in THP-1 macrophage derived foam cells, which may be related to the TLR4/NF-κB dependent and LXRα-independent pathway.