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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/31726

    標題: Medroxyprogesterone acetate drives M2 macrophage differentiation toward a phenotype of decidual macrophage
    作者: Tsai, Yung-Chieh
    Tseng, Joseph T.
    Wang, Chia-Yih
    Su, Mei-Tsz
    Huang, Jyun-Yuan
    Kuo, Pao-Lin
    貢獻者: Chi Mei Med Ctr, Dept Obstet & Gynecol
    Natl Cheng Kung Univ Hosp, Dept Obstet & Gynecol
    Natl Cheng Kung Univ, Dept Biotechnol & Bioind Sci
    Natl Cheng Kung Univ, Dept Cell Biol & Anat, Coll Med
    Chia Nan Univ Pharm & Sci, Dept Sport Management
    關鍵字: Medroxyprogesterone acetate
    日期: 2017-09-05
    上傳時間: 2018-11-30 15:54:23 (UTC+8)
    出版者: Elsevier Ireland Ltd
    摘要: M1 macrophage differentiation plays a crucial role in enhanced inflammation during pregnancy, which may lead to pregnancy complications. Therefore, modulation of macrophage differentiation toward the M2 phenotype is desirable to ensure a successful pregnancy. Medroxyprogesterone acetate (MPA) is a potent progestin with an anti-inflammatory property, but its effect on macrophage differentiation is unknown. This study aimed to examine whether MPA can induce an M2 macrophage differentiation by using the human monocytes cell line THP-1 or primary monocytes. THP-1 cells were primed with phorbol-12-myristate-13 acetate (PMA) to initiate macrophage differentiation. By incubating with MPA, the cells (denoted as MPA-pTHP-1) underwent M2 macrophage differentiation with downregulations of CD11c, 1 beta and TNF-alpha, and upregulations of CD163 and IL-10; while cells incubated with progesterone (P4) did not show the M2 phenotype. Primary monocytes treated with MPA also had the same M2 phenotype. Moreover, M1 macrophages derived from IFN-gamma/LPS-treated THP-1 cells, which had high levels of IL-lb and iNOS, and low levels of IL-10 and IDO, were reversed to the M2 phenotype by the MPA treatment. We also found that the MPA-pTHP-1 promoted the decidualization of endometrial stromal cells and the invasion of trophoblast cells. To mimic conditions of exposure to various pathogens, MPA-pTHP-1 cells were stimulated by different types of TLR ligands. We found they produced lower levels of IL-10 and TNF-alpha, as well as a higher level of IL-10, compared to untreated cells. Finally, we found the level of phosphorylated ERR in the MPA-pTHP-1 cells was increased, but its IL-10 production was suppressed by either the progesterone/glucocorticoid antagonist (Mifepristone) or MEK inhibitor (U0126). Taken together, MPA could drive monocyte differentiation toward an M2 phenotype that mimics decidual macrophages. This finding holds great potential to combat chronic endometrial inflammation. (C) 2017 Elsevier B.V. All rights reserved.
    關聯: Molecular and Cellular Endocrinology, v.452, n.C, pp.74-83
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