Effect of tumor necrosis factor-it on the expression of ATP binding cassette transporter A1 in THP-1 macrophage foam ceils / 中华老年医学杂志

ABSTRACT

Objective To investigate the influence of tumor necrosis factor-?(TNF-?) on ATP binding cassette transporter A1(ABCA1)in THP-1 macrophage foam cells, and the intervention effect of nuclear factor-?B(NF-?B) inhibitor TPCK on the TNF-?, so as to determine the role of TNF-?/ NF-?B in cellular cholesterol efflux. Methods Foam cells were transformed from THP1 cells. The correlation of cellular cholesterol efflux from foam cells with different concentrations and time stimulated by TNF-? were estimated. Subsequently foam cells were treated with TNF-? at satulated concentration(10.0 ng/ml ), TPCK(10?mol/L),or TPCK(10?mol/L) pretreated for 60 min before TNF-? stimulation. ABCA1 gene expression was analyzed by RT-PCR. ABCA1 protein level was detected by Western blot. Results TNF-? decreased cellular cholesterol efflux of foam cells in concentration-and time-dependent manner. 10 ng/ml of TNF-? down-regulated the levels of both ABCA1 mRNA and protein expressions in time-dependent manner. TPCK was observed to efficiently block the suppressive effect of TNF-? on ABCA1. Conclusions TNF-? decreases cellular cholesterol efflux mainly through the down-regulation of ABCA1. TPCK, an inhibitor of NF-?B activation, is observed to partly block the suppressive effect of TNF-? on ABCA1, suggesting a mechanism involving NF-?B signal transduction. TNF-?/NF-?B might play a critical role in the progression of atherosclerosis by decreasing cellular cholesterol efflux from foam cells.