Induction of macrophage scavenger receptor type BI expression by tamoxifen and 4-hydroxytamoxifen
Induction of macrophage scavenger receptor type BI expression by tamoxifen and 4-hydroxytamoxifen
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他莫昔芬和4-羟基他莫昔芬诱导巨噬细胞清道夫受体BI型表达
DOI：
10.1016/j.atherosclerosis.2011.06.048
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发表时间：
2011-10-01
期刊：
影响因子：
5.3
通讯作者：
Han, Jihong
中科院分区：
文献类型：
--
作者：
Dong, Pengzhi;Xie, Tao;Han, Jihong
目的：清道夫受体BI(SR-BI)是一种由巨噬细胞表达的高密度脂蛋白受体。SR-BI的表达与动脉粥样硬化的发生发展密切相关。他莫昔芬已被证明具有动脉粥样硬化保护作用。方法与结果：在本研究中，我们观察了他莫昔芬和4-羟基他莫昔芬对巨噬细胞SR-BI表达的影响。以野生型小鼠巨噬细胞系和腹膜巨噬细胞为研究对象，观察他莫昔芬和4-羟基他莫昔芬对巨噬细胞SR-BI基因和蛋白表达的影响。我们观察到，他莫昔芬和4-羟基他莫昔芬增加了雌性小鼠巨噬细胞系(J774细胞)SR-BI蛋白的表达，但不能增加雄性小鼠巨噬细胞系(原始细胞)的SR-BI蛋白表达。在从野生型雄性和雌性小鼠分离的初级巨噬细胞中也得到了类似的观察。因此，他莫昔芬和4-羟基他莫昔芬诱导巨噬细胞SR-BI的表达具有性别依赖性。此外，我们观察到SR-BI的表达是通过激活雌激素受体(ER，特别是ERα)来诱导的，但通过失活ER来抑制。然而，巨噬细胞SR-BI蛋白表达的增加不依赖于转录，因为SR-BI的mRNA表达和启动子活性不受他莫昔芬和4-羟基他莫昔芬的影响。相反，他莫昔芬增加了巨噬细胞SR-BI蛋白的稳定性。他莫昔芬对小鼠肝脏SR-BI蛋白表达无影响，但可改善血脂谱。结论：我们的研究表明，他莫昔芬和4-羟基他莫昔芬通过转录后机制诱导巨噬细胞SR-BI蛋白表达。(C)2011爱思唯尔爱尔兰有限公司。保留所有权利。
Objective: Scavenger receptor type BI (SR-BI) is an HDL receptor that is expressed by macrophages. SR-BI expression is tightly linked to the development of atherosclerosis. Tamoxifen has been shown to be atheroprotective. However, the involved mechanisms have not been fully elucidated.Methods and results: In this study, we investigated the effect of tamoxifen and 4-hydroxytamoxifen on macrophage SR-BI expression. Macrophage cell lines and peritoneal macrophages isolated from wild-type mice were used to determine changes in SR-BI mRNA and protein expression in response to tamoxifen and 4-hydroxytamoxifen. We observed that tamoxifen and 4-hydroxytamoxifen increased SR-BI protein expression in a macrophage cell line derived from female mice (J774 cells) but not in a line derived from male mice (RAW cells). Similar observations were obtained in primary macrophages isolated from wild-type male and female mice. Thus, the induction of macrophage SR-BI expression by tamoxifen and 4-hydroxytamoxifen is sex-dependent. Furthermore, we observed that SR-BI expression was induced by activating the oestrogen receptor (ER, specifically ER alpha) but was inhibited by inactivating the ER. However, the increased macrophage SR-BI protein expression was independent of transcription because SR-BI mRNA expression and promoter activity were not influenced by tamoxifen and 4-hydroxytamoxifen. Instead, tamoxifen increased the stability of macrophage SR-BI protein. Tamoxifen administration to mice had no effect on hepatic SR-BI protein expression but improved the serum lipid profile.Conclusion: Our study demonstrates that tamoxifen and 4-hydroxytamoxifen induce macrophage SR-BI protein expression via a post-transcriptional mechanism. (C) 2011 Elsevier Ireland Ltd. All rights reserved.