Effect of Helixor A on Natural Killer Cell Activity in Endometriosis

Abstract

Background and Aim: NK cells are one of the major immune cells in endometriosis pathogenesis. While previous clinical studies have shown that helixor A to be an effective treatment for endometriosis, little is known about its mechanism of action, or its relationship with immune cells. The aim of this study is to investigate the effects of helixor A on Natural killer cell (NK cell) cytotoxicity in endometriosisMaterials and Methods: We performed an experimental study. Samples of peritoneal fluid were obtained from January 2011 to December 2011 from 50 women with endometriosis and 50 women with other benign ovarian cysts (control). Peritoneal fluid of normal control group and endometriosis group was collected during laparoscopy. Baseline cytotoxicity levels of NK cells were measured with the peritoneal fluid of control group and endometriosis group. Next, cytotoxicity of NK cells was evaluated before and after treatment with helixor A. NK-cell activity was determined based upon the expression of CD107a, as an activation marker.Results: NK cells cytotoxicity was 79.38±2.13% in control cells, 75.55±2.89% in the control peritoneal fluid, 69.59±4.96% in endometriosis stage I/II endometriosis, and 63.88±5.75% in stage III/IV endometriosis. A significant difference in cytotoxicity was observed between the control cells and stage III/IV endometriosis, consistent with a significant decrease in the cytotoxicity of NK cells in advanced stages of endometriosis; these levels increased significantly after treatment with helixor A; 78.30% vs. 86.40% (p = 0.003) in stage I/II endometriosis, and 73.67% vs. 84.54% (p = 0.024) in stage III/IV. The percentage of cells expressing CD107a was increased significantly in each group after helixor A treatment; 0.59% vs. 1.10% (p = 0.002) in stage I/II endometriosis, and 0.79% vs. 1.40% (p = 0.014) in stage III/IV.Conclusions: Helixor A directly influenced NK-cell cytotoxicity through direct induction of CD107a expression. Our results open new role of helixor A as an imune modulation therapy, or in combination with hormonal agents, for the treatment of endometriosis.

Involvement of immune cells in the pathogenesis of endometriosis

“…With regard to endometriosis, the cytotoxic function is reduced in peripheral and peritoneal NK cells. [53][54][55][56][57] Due to diminished cytotoxicity, retrograde endometrial cells are prone to survive in the peritoneal cavity, which results in the development of endometriosis. Factors controlling NK cell function have not been thoroughly investigated; however, several studies have shown that IL-6, 57 IL-15, 58 and transforming growth factor-β1 59 suppress NK cell cytotoxic activity.…”

“…60 Further, an extract of the white mistletoe tree, Helixor A, also directly activates NK cell cytotoxicity. 56 By adapting a strategy for cancer immunotherapy, 61 Montenegro et al administered intraperitoneal injections of IL-2-activated NK cells and reduced lesion formation in a mouse endometriosis model. 62 In this manner, progress in developing cancer immunotherapies may provide new therapeutic options for endometriosis, and further development is expected.…”

“…With regard to endometriosis, the cytotoxic function is reduced in peripheral and peritoneal NK cells . Due to diminished cytotoxicity, retrograde endometrial cells are prone to survive in the peritoneal cavity, which results in the development of endometriosis.…”

“…conducted mouse model experiments and found that the oral administration of probiotics activates peritoneal NK cells, and reduces endometriotic lesion formation . Further, an extract of the white mistletoe tree, Helixor A, also directly activates NK cell cytotoxicity . By adapting a strategy for cancer immunotherapy, Montenegro et al .…”

Decreased Cytotoxicity of Peripheral and Peritoneal Natural Killer Cell in Endometriosis

“…Markers of NK cell cytotoxicity include the natural receptors NKp46, NKp44, and NKG2D, CD16 (a cell surface marker), and CD107a [ 42 ] and CD69 (markers of activation). The levels of all of these markers are significantly reduced in the peritoneal NK cells of endometriosis patients.…”