Retinoid X receptor agonists inhibit phorbol-12-myristate-13-acetate (PMA)-induced differentiation of monocytic THP-1 cells into macrophages
Retinoid X receptor agonists inhibit phorbol-12-myristate-13-acetate (PMA)-induced differentiation of monocytic THP-1 cells into macrophages
复制标题
类维生素A X 受体激动剂抑制佛波醇-12-肉豆蔻酸-13-乙酸酯 (PMA) 诱导的单核 THP-1 细胞向巨噬细胞的分化
DOI：
10.1007/s11010-009-0278-z
复制
发表时间：
2010-02-01
影响因子：
4.3
通讯作者：
He, Ben
中科院分区：
文献类型：
--
作者：
Zhou, Lei;Shen, Ling-hong;He, Ben
单核/巨噬细胞分化是动脉粥样硬化发展过程中的一个重要过程。维甲酸X受体(RXR)是核激素受体超家族的一员，在包括动脉粥样硬化在内的许多代谢紊乱中起着重要的调节作用。本研究旨在探讨RXR激动剂在体外对单核/巨噬细胞分化的影响。在RXR激动剂存在或不存在的情况下，用佛波醇-12-肉豆蔻酸酯-13-醋酸酯(PMA)孵育THP-1细胞系，使其分化为巨噬细胞样表型。用四甲基偶氮唑盐比色法测定贴壁分化的THP-1细胞的存活率。用流式细胞仪检测巨噬细胞表面标志物CD11b和CD36。用荧光标记的胶乳微球测定吞噬功能。用双抗体夹心酶联免疫吸附试验检测细胞因子α、α、IL-12p70和基质金属蛋白酶-9的表达。在RXR激动剂9-顺式维甲酸或SR11237存在下，PMA诱导的THP-1细胞黏附减少，巨噬细胞样形态改变减少，细胞表面抗原CD11b和CD36表达减少，并下调乳胶珠的吞噬功能和肿瘤坏死因子-α和基质金属蛋白酶-9的产生。提示RXR激动剂可抑制PMA诱导的THP-1细胞向巨噬细胞样细胞分化，这可能有助于了解RXR及其激动剂的抗动脉粥样硬化作用。
Monocyte/macrophage differentiation is an essential process during atherosclerosis development. The retinoid X receptor (RXR) is a member of the nuclear hormone receptor superfamily, which plays an important regulatory role in many metabolic disorders, including atherosclerosis. The purpose of this study was to investigate the effect of RXR agonist on monocyte/macrophage differentiation in vitro. The THP-1 cell line was differentiated into a macrophage-like phenotype by incubation with phorbol-12-myristate-13-acetate (PMA) in the presence or absence of RXR agonist. The viability of adherent differentiated THP-1 cells was determined by MTT assay. Macrophage surface marker CD11b and CD36 was analyzed by flow cytometry. Phagocytosis was measured by fluorescence-labeled latex beads. The production of Cytokine Tunlornecrosisfactor-α (TNF-α), Interlaken-12p70 (IL-12p70), and Matrix metalloproteinase-9 (MMP-9), each of which was analyzed by ELISA. In the presence of the RXR agonists 9-cis retinoic acid or SR11237, PMA-induced THP-1 cells became less adherent, showed decreased macrophage-like morphological changes, decreased cell surface antigen CD11b and CD36 expression, and down regulated the phagocytosis of latex beads and the production of TNF-α and MMP-9. These data suggest that RXR agonists inhibit PMA-induced THP-1 cell differentiation into macrophage-like cells, which may be helpful in understanding the anti-atherosclerotic effect of RXR and its agonists.