The effect of mifepristone on the peripheral blood natural killer cell's cytotoxicity and expression of CD94/NKG2A and NKG2D during the implantation phase

Chen, Xiuying; Zhuang, Yaling; Li, Li; Zhang, Wu-Wen; Huang, Lili

doi:10.1016/j.fertnstert.2009.09.015

Cited by 10 publications

(5 citation statements)

References 40 publications

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“…Following co-culture, the viability of the target K562 cells was determined by the MTS assay according to the manufacturer's protocol. The percentage of cytolysis was calculated as: [1−(experimental group OD−effector cell OD)/target cell OD]×100% [25], [26], where OD is the optical density.…”

Section: Methodsmentioning

confidence: 99%

Mifepristone Increases the Cytotoxicity of Uterine Natural Killer Cells by Acting as a Glucocorticoid Antagonist via ERK Activation

et al. 2012

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BackgroundMifepristone (RU486), a potent antagonist of progesterone and glucocorticoids, is involved in immune regulation. Our previous studies demonstrated that mifepristone directly augments the cytotoxicity of human uterine natural killer (uNK) cells. However, the mechanism responsible for this increase in cytotoxicity is not known. Here, we explored whether the increased cytotoxicity in uNK cells produced by mifepristone is due to either anti-progesterone or anti-glucocorticoid activity, and also investigated relevant changes in the mitogen-activated protein kinase (MAPK) pathway.Methodology/Principal FindingsUterine NK cells were isolated from decidual samples and incubated with different concentrations of progesterone, cortisol, or mifepristone. The cytotoxicity and perforin expression of uNK cells were detected by mitochondrial lactate dehydrogenase-based MTS staining and flow cytometry assays, respectively. Phosphorylation of components of the MAPK signaling pathway was detected by Western blot. Cortisol attenuated uNK cell-mediated cytotoxicity in a concentration-dependent manner whereas progesterone had no effect. Mifepristone alone increased the cytotoxicity and perforin expression of uNK cells; these effects were blocked by cortisol. Furthermore, mifepristone increased the phosphorylation of ERK1/2 in a cortisol-reversible manner. Specific ERK1/2 inhibitor PD98059 or U0126 blocked cortisol- and mifepristone-induced responses in uNK cells.Conclusions/SignificanceThese results suggest that mifepristone acts as a glucocorticoid antagonist to augment uNK cell-mediated cytotoxicity via ERK activation, which may be caused by increased perforin expression. These observations may reveal an important mechanism by which mifepristone upregulates the cytotoxicity of uNK cells.

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Section: Methodsmentioning

confidence: 99%

Mifepristone Increases the Cytotoxicity of Uterine Natural Killer Cells by Acting as a Glucocorticoid Antagonist via ERK Activation

et al. 2012

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“…The relationship between increase in peripheral blood NK cells and reproductive failure is one of the common controversial subjects in reproductive medicine (18). NK cells are an abundant population of lymphocyte in the decidual, and are thus expected to play a physiological role during the implantation process; however, despite many similarities between the two groups of NK cells in peripheral blood and decidua, there are some differences (9).…”

Section: Discussionmentioning

confidence: 99%

The Role of CD16+, CD56+, NK (CD16+/CD56+) and B CD20+ Cells in the Outcome of Pregnancy in Women with Recurrent Spontaneous Abortion

Boroujerdnia¹,

Neda²,

Ailin³

et al. 2015

IJWHR

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“…However, hypercortosolism can be treated with mifepristone (RU486), the only glucocorticoid receptor (GR) antagonist that is availabe for clinical use [ 129 ] ( Table 1 ). In two sutdies, Chen et al, demonstrated that isolated human uterine as well as peripheral blood NK cells showed increased cytoxicity against K562s in the presence of mifepristone, aborgating the immunosuppressive effects of cortisol exposure [ 133 , 134 ]. Morever, mice that underwent LPS-induced immunosuppression had restored humoural and T-cell anti-tumor responses as well as improved tumor clearance when treated with mifepristone (30 mg/kg; i.p.)…”

Section: The Evidence: Understanding the Mechanisms Of Postoperative Natural Killer Cell Suppressionmentioning

confidence: 99%

Postoperative Natural Killer Cell Dysfunction: The Prime Suspect in the Case of Metastasis Following Curative Cancer Surgery

Market

Tennakoon

Auer

2021

IJMS

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Surgical resection is the foundation for the curative treatment of solid tumors. However, metastatic recurrence due to the difficulty in eradicating micrometastases remain a feared outcome. Paradoxically, despite the beneficial effects of surgical removal of the primary tumor, the physiological stress resulting from surgical trauma serves to promote cancer recurrence and metastasis. The postoperative environment suppresses critical anti-tumor immune effector cells, including Natural Killer (NK) cells. The literature suggests that NK cells are critical mediators in the formation of metastases immediately following surgery. The following review will highlight the mechanisms that promote the formation of micrometastases by directly or indirectly inducing NK cell suppression following surgery. These include tissue hypoxia, neuroendocrine activation, hypercoagulation, the pro-inflammatory phase, and the anti-inflammatory phase. Perioperative therapeutic strategies designed to prevent or reverse NK cell dysfunction will also be examined for their potential to improve cancer outcomes by preventing surgery-induced metastases.

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The effect of mifepristone on the peripheral blood natural killer cell's cytotoxicity and expression of CD94/NKG2A and NKG2D during the implantation phase

Cited by 10 publications

References 40 publications

Mifepristone Increases the Cytotoxicity of Uterine Natural Killer Cells by Acting as a Glucocorticoid Antagonist via ERK Activation

Mifepristone Increases the Cytotoxicity of Uterine Natural Killer Cells by Acting as a Glucocorticoid Antagonist via ERK Activation

The Role of CD16+, CD56+, NK (CD16+/CD56+) and B CD20+ Cells in the Outcome of Pregnancy in Women with Recurrent Spontaneous Abortion

Postoperative Natural Killer Cell Dysfunction: The Prime Suspect in the Case of Metastasis Following Curative Cancer Surgery

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