Medroxyprogesterone acetate drives M2 macrophage differentiation toward a phenotype of decidual macrophage
| Autor: | Pao Lin Kuo, Chia Yih Wang, Mei Tsz Su, Yung Chieh Tsai, Jyun Yuan Huang, Joseph T. Tseng |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Stromal cell THP-1 Cells Primary Cell Culture Nitric Oxide Synthase Type II CD11c Inflammation Medroxyprogesterone Acetate Biology Biochemistry Monocytes 03 medical and health sciences Hormone Antagonists 0302 clinical medicine Endocrinology Pregnancy Internal medicine Nitriles Butadienes Decidua medicine Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Macrophage Enzyme Inhibitors Molecular Biology 030219 obstetrics & reproductive medicine Macrophages Decidualization Cell Differentiation M2 Macrophage Trophoblasts Mifepristone 030104 developmental biology Monocyte differentiation Cancer research Cytokines Tetradecanoylphorbol Acetate Female Stromal Cells medicine.symptom Endometritis CD163 |
| Zdroj: | Molecular and Cellular Endocrinology. 452:74-83 |
| ISSN: | 0303-7207 |
| DOI: | 10.1016/j.mce.2017.05.015 |
| Popis: | 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, IL-1β and TNF-α, 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-γ/LPS-treated THP-1 cells, which had high levels of IL-1b 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-1β and TNF-α, as well as a higher level of IL-10, compared to untreated cells. Finally, we found the level of phosphorylated ERK 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. |
| Databáze: | OpenAIRE |
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