肿瘤坏死因子α对乙酰辅酶A:胆固醇酰基转移酶1基因表达的影响

Influence of TNF-α on the expression of acyl coenzyme A: cholesteryl acyltransferase 1

目的研究泡沫细胞形成过程中肿瘤坏死因子-α(TNF-α)对乙酰辅酶A:胆固醇酰基转移酶1(ACAT1)基因的影响。方法体外培养人THP-1单核细胞系,由佛波酯作用使其分化为巨噬细胞,再由乙酰化低密度脂蛋白作用转变为泡沫细胞。TNF-α分别作用于上述三种细胞24 h,用W estern b lot法检测ACAT1蛋白表达,RT-PCR法检测ACAT1 mRNA水平。结果在单核细胞分化为巨噬细胞及转变为泡沫细胞的过程中,ACAT1蛋白及mRNA均增加(P均<0.05);TNF-α可上调三种细胞ACAT1蛋白表达及mRNA水平(P均<0.05)。结论单核细胞分化为巨噬细胞及转变为泡沫细胞的过程中,ACAT1基因表达明显增加,TNF-α可明显促进ACAT1基因表达。

[ Objective] To study the effects of tumor necrosis factor-α（TNF-α） on the expression of the acyl coenzyme A： cholesteryl acyltransferase 1 （ACAT1） during the formation of foam cells. [ Methods] THP-1 human monocytic leukemia cells （ THP-1 ） were cultured. The differentiation of THP-1 cells into macrophages （MPs） was induced by phorbol esters （PMA）. The MPs were incubated with acyl-low density lipoprotein （Ac-LDL） to generate foam cells （FCs）. TNF-α（60 ng/mL） was added in those three kinds of cells and incubated for 24 hours. The levels of ACAT1 protein and mRNA were detected by western blotting and RT-PCR. [ Results ] The ACAT1 protein and ACAT1 mRNA were significantly increased during the differentiation of monocytes into macrophages and the formation of foam cells （ P 〈 0.05 ）. TNF-α stimulated the expression of ACAT1 protein and ACAT1 mRNA （P 〈 0.05 ）. [ Conclusion ] The ACAT1 gene expression is up-regulated during the differentiation of monocytes into macrophages and the formation of foam cells. TNF-α significantly increases the expression of ACAT1 gene.