Marked induction of sterol 27-hydroxylase activity and mRNA levels during differentiation of human cultured monocytes into macrophages
Marked induction of sterol 27-hydroxylase activity and mRNA levels during differentiation of human cultured monocytes into macrophages
复制标题
DOI：
10.1016/s0167-4889(02)00398-1
复制
发表时间：
2003-02-17
影响因子：
5.1
通讯作者：
Babiker, A
中科院分区：
文献类型：
--
作者：
Hansson, M;Ellis, E;Babiker, A
甾醇27-羟基酶被认为参与了从巨噬细胞和早期动脉粥样硬化病变中清除胆固醇的另一种途径。我们先前已经证明，人肺巨噬细胞以及单核细胞来源的巨噬细胞具有相对较高的甾醇27-羟基酶(CyP27)活性。这种酶将细胞内的胆固醇转化为27-羟基胆固醇和胆汁酸，后者从培养细胞流入培养基中。结果表明，人单核细胞具有很低的细胞色素P27活性和细胞色素P27基因表达水平。在向巨噬细胞分化的过程中，在无血清培养4天后，细胞色素P27活性和细胞色素P27基因表达水平均显著升高。添加巨噬细胞集落刺激因子对诱导作用无明显影响，添加胎牛血清则有抑制作用。胆固醇合成。被发现是在无血清培养的巨噬细胞产生27个含氧产物的关键因素。分化细胞清除细胞内胆固醇的能力增强是有意义的，并支持细胞色素P27是一种抗动脉粥样硬化因子的论点。(C)2002 Elsevier Science B.V.保留所有权利。
Sterol 27-hydroxylase has been suggested to be involved in an alternative pathway for the elimination of cholesterol from macrophages and early atherosclerotic lesions. We have previously shown that human lung macrophages as well as monocyte-derived macrophages have a relatively high activity of sterol 27-hydroxylase (CYP27). This enzyme converts intracellular cholesterol into 27-hydroxycholesterol and cholestenoic acid that flux from cultured cells into the medium. It is shown here that human monocytes have very low CYP27 activity and CYP27 mRNA levels. During differentiation into macrophages, both CYP27 activity and CYP27 mRNA levels increase markedly after 4 days of culture in serum-free medium. Addition of macrophage-colony stimulating factor had no significant effect on the induction and addition of fetal calf serum had an inhibitory effect. Cholesterol synthesis. was found to be a critical factor for the production of 27-oxygenated products by the macrophages cultured in serum-free medium. The increased capacity of the differentiated cells to eliminate intracellular cholesterol is of interest and supports the contention that CYP27 is an antiatherogenic factor. (C) 2002 Elsevier Science B.V. All rights reserved.