Low-dose SKA Progesterone and Interleukin-10 modulate the inflammatory pathway in endometriotic cell lines

Objective To study the efficacy of low-dose SKA Progesterone and IL-10 in modulating the inflammatory pathway in endometriosis. Design Experimental basic science study. Setting Reproductive biology laboratory. Models Immortalized human endometriotic epithelial cells (12Z) derived from active red peritoneal lesions, immortalized human endometriotic stromal cells (22B) derived from active red peritoneal lesions and immortalized human endometrial cell line T-Hesc (ATCC collection). Methods Cells were treated with SKA-Progesterone and SKA-IL10 at low doses (10pg/ml and 10fg/ml respectively). Medroxyprogesterone 17-acetate (MPA) was used at a dose of 10μM as reference treatment. Main outcome measure(s) Modulation of HSD17B1 levels by WB analysis after low-dose SKA Progesterone and MPA; Modulation of IKBα protein levels and NF-kB p65 nuclear levels by WB analysis after low-dose SKA-Progesterone, low-dose SKA-IL10, low-dose SKA-Progesterone and low-dose SKA-IL10 (combined treatment), MPA. Results Low-dose SKA Progesterone was effective in the inhibition of HSD17B1 expression in endometriotic epithelial (12Z) and stromal (22B) cell lines. Low-dose of SKA Progesterone and low-dose of SKA-IL10 inhibit NF-kB p65 nuclear localization and DNA binding in endometriotic epithelial (12Z) cells, stromal (22B) cells line and in endometrial cell line T-Hesc. The combined treatment showed an additive effect, namely increasing the inhibition of nuclear localization of NF-kB p65 and DNA binding as result of single treatments. Conclusion Our data suggest that the use of a combination of low-dose SKA Progesterone and IL-10 may represent an opportunity for the development of new therapies in the clinical management of endometriosis.