Progesterone enhances macrophage colony-stimulating factor production in human endometrial stromal cells in vitro.

Hatayama, Hiroshi; Kanzaki, Hideharu; Iwai, Mieko; Kariya, Masatoshi; Fujimoto, Mai; Higuchi, T; Kojima, Kenji; Nakayama, Hiroki; Mori, Takahide; Fujita, Jun

doi:10.1210/endo.135.5.7956912

Cited by 43 publications

(23 citation statements)

References 17 publications

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“…Accordingly, increased local and circulating GM-CSF levels have been associated with preeclampsia, an inflammatory placenta disorder (65,66), although other reports failed to demonstrate such associations (67,68). Our results suggest that the balance between M-CSF and GM-CSF at the fetal-maternal interface needs to be strictly regulated, which might be done, at least in part, by progesterone, which has been shown to upregulate M-CSF and downregulate GM-CSF (53,69). It is also notable that IL-10, but not the Th2 cytokines IL-4 and IL-13, was able to restore the GM-CSF-mediated inhibition of the decidual Mf phenotype, supporting the concept of an M-CSF-and IL-10-driven homeostatic and tolerogenic, rather than a Th2-dominated, local environment in early pregnancy.…”

Section: Discussionmentioning

confidence: 49%

“…Similarly, IL-10 is constitutively produced by a variety of cells and is also induced in inflammatory conditions to counteract proinflammatory cytokines, thereby considered as an important homeostatic mechanism to avoid inappropriate T cell activation (49). In the context of pregnancy, IL-10 is locally produced by, for example, trophoblasts, uterine NK cells, and Mf (22,50,51), and M-CSF, which increases dramatically in the mouse and human uterus during gestation (26,28), is produced by, for example, endometrial stromal cells, trophoblasts, and uterine NK cells (52,53). Thus, it is likely that the locally produced M-CSF and IL-10 promote homeostatic Mf with the ability of clearing infections without compromising fetal tolerance.…”

Section: Discussionmentioning

confidence: 99%

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Macrophages at the Fetal–Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10

Svensson

Jenmalm

Matussek

et al. 2011

The Journal of Immunology

309

314

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During pregnancy, the maternal immune system is challenged by the presence of the fetus, which must be tolerated despite being semiallogeneic. Uterine mucosal (or decidual) macrophages (Mϕ), one of the major leukocyte populations at the fetal–maternal interface, have been implicated in fetal tolerance, but information regarding their regulation is scarce. In this study, we investigated the role of several factors potentially involved in the differentiation and polarization of decidual Mϕ with an in vitro Mϕ differentiation model. By using flow cytometry, we showed that M-CSF and IL-10 were potent inducers of M2 (immunoregulatory) Mϕ markers expressed on human decidual Mϕ (CD14, CD163, CD206, CD209). In contrast, proinflammatory stimuli, and unexpectedly also the Th2-associated IL-4 and IL-13, induced different patterns of expression, indicating that a Th2-dominated environment is not required for decidual Mϕ polarization. M-CSF/IL-10–stimulated and decidual Mϕ also showed similar cytokine secretion patterns, with production of IL-10 as well as IL-6, TNF, and CCL4. Conversely, the proinflammatory, LPS/IFN-γ–stimulated Mϕ produced significantly higher levels of TNF and no IL-10. We also used a gene array with 420 Mϕ-related genes, of which 100 were previously reported to be regulated in a global gene expression profiling of decidual Mϕ, confirming that M-CSF/IL-10–induced Mϕ are closely related to decidual Mϕ. Taken together, our results consistently point to a central role for M-CSF and in particular IL-10 in the shaping of decidual Mϕ with regulatory properties. These cytokines may therefore play an important role in supporting the homeostatic and tolerant immune milieu required for a successful pregnancy.

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Macrophages at the Fetal–Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10

Svensson

Jenmalm

Matussek

et al. 2011

The Journal of Immunology

309

314

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“…The inhibitory effects of danazol on ESC activation into G-CSF-secreting cells are opposite to the effects of M-CSF, which induces ESC activation into G-CSF-secreting cells. M-CSF is produced in the human endometrium, particularly by decidual cells (33,34). IL-8 secretion by ESCs is regulated by endometrial IL-1 and IL-1 receptor antagonist (31).…”

Section: Discussionmentioning

confidence: 99%

Danazol regulates the functions of normal human endometrial stromal cell subpopulations by modifying endometrial cytokine networks

Tanaka

2009

Int J Mol Med

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Abstract. Local danazol therapy can improve endometriotic signs and symptoms without causing any menstrual disorders. As a consequence, certain direct actions of danazol on endometriotic tissues have been proposed, but the mechanisms of these actions have not been clarified. In the present study, the direct effects of danazol on normal human endometrial stromal cells (ESCs) were examined using in vitro decidualization assays. Danazol did not affect the viable cell numbers of unstimulated ESCs or 8Br-cAMP-stimulated decidualized ESCs, but significantly enhanced the viable cell numbers of 8-Br-cAMP-stimulated ESCs during decidualization in a dose-dependent manner. Danazol had no effect on PRL secretion by 8-Br-cAMP-stimulated decidualized ESCs. Danazol, as well as progesterone and medroxyprogesterone acetate (MPA), induced ESC decidualization. Danazol synergistically enhanced the differentiation process of 8-BrcAMP-stimulated ESCs during decidualization. Although progesterone and MPA increased G-CSF and IL-8 secretion by ESCs in similar manner to 8-Br-cAMP, danazol had no such effects. Moreover, remarkable increases in G-CSF and IL-8 secretions by 8-Br-cAMP-stimulated ESCs during decidualization were completely inhibited by cotreatment with danazol. These results indicate that danazol has specific pharmacological effects on ESCs, rather than progesteronelike effects or similar effects to those reported for endometrial cytokines. According to the results, normal human ESCs can be classified into at least four functional subpopulations. Therefore, under certain circumstances, danazol has similar or opposite effects on ESCs to certain endometrial cytokines, suggesting that it regulates functional cellular subpopulation ratios of normal human ESCs by modifying the endometrial cytokine network in endometrial stromal tissues.

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“…A number of researchers have reported that M-CSF and its receptor are expressed in the female reproductive tract and that M-CSF plays an important role in pregnancy in mice [1,2,[21][22][23], humans [8,[11][12][13], pigs [35] and cows [3,17,19]. Furthermore, M-CSF concentrations in maternal peripheral blood during the estrous cycle and pregnancy have been reported in humans and mice.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, human endometrial, decidual and placental tissues have been found to express M-CSF mRNA and have demonstrated extractable immunoreactive M-CSF [8,12,13]. Human M-CSF, in a concentration-dependent manner, increases the secretion of human chorionic gonadotropin from primary cultured human cytotrophoblastic cells and a human placental cell line [27].…”

mentioning

confidence: 97%

Concentration of Macrophage Colony-Stimulating Factor (M-CSF) in Bovine Peripheral Blood during Pregnancy

Oshima

Kojima

Komatsu

et al. 2008

The Journal of Veterinary Medical Science

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ABSTRACT. Macrophage colony-stimulating factor (M-CSF) is a hemopoietic cytokine with a primary role in placental physiology. Gene expression of M-CSF in the bovine endometrium shows a temporal upward trend during early and mid pregnancy. This study determined the plasma M-CSF levels during pregnancy using ELISA. In experiment 1, to investigate the relationship between the concentration of M-CSF in peripheral blood and pregnancy, the plasma M-CSF levels were determined in 125 pregnant and 21 non-pregnant Japanese Black cows. The pregnant animals were divided into nine groups based on the month of pregnancy. An ELISA for bovine M-CSF established previously was used according to the authors' instructions. In experiment 2, the plasma M-CSF level was determined to investigate the temporal changes in its concentration in the peripheral blood during pregnancy. In experiment 1, the plasma M-CSF level varied from month to month during pregnancy; the mean level in the first-month of pregnancy was significantly higher than those in the third and last months of pregnancy and non-pregnancy (P<0.05). In experiment 2, the plasma M-CSF level varied with the day of pregnancy (P<0.05). The mean level of plasma M-CSF decreased gradually until 6 weeks of pregnancy; it appeared to increase during weeks 7-9, then varied with several small peaks until 27 weeks of pregnancy and finally decreased gradually until parturition. These results suggest that the plasma M-CSF level may be related to changes in the uterus and placenta as pregnancy progresses.

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Progesterone enhances macrophage colony-stimulating factor production in human endometrial stromal cells in vitro.

Cited by 43 publications

References 17 publications

Macrophages at the Fetal–Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10

Macrophages at the Fetal–Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10

Danazol regulates the functions of normal human endometrial stromal cell subpopulations by modifying endometrial cytokine networks

Concentration of Macrophage Colony-Stimulating Factor (M-CSF) in Bovine Peripheral Blood during Pregnancy

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