ECE2018 Guided Posters Female Reproduction (11 abstracts)
Low-dose SKA Progesterone and Interleukin-10 modulate the inflammatory pathway in endometriotic cell lines
Francesca Mancini 1 , Domenico Milardi 2 , Piero Carfagna 3 , Giuseppe Grande 1 , Vincenzo Miranda 4 , Alessandra De Cicco Nardone 3 , Domenico Ricciardi 3 , Alfredo Pontecorvi 1, , Riccardo Marana 1 & Fiorenzo De Cicco Nardone 3
1International Scientific Institute “Paul VI”, Rome, Italy; 2Division of Endocrinology, Fondazione Policlinico “A. Gemelli”, Rome, Italy; 3Department of Obstetrics and Gynecology, Fondazione Policlinico “A. Gemelli”, Rome, Italy; 4Clinical Research Unit, GUNA S.p.a., Milan, Italy.
Endometriosis is a chronic gynecological inflammatory disease characterized by the presence of functional endometrial glands and stroma outside of the uterine cavity. It affects 7–10% of women of reproductive age, up to 50% of women with infertility and up to 60% of women with dysmenorrhea. The aim of this pre-clinical study was evaluate the efficacy of low-dose SKA Progesterone (GUNA) and low-dose SKA IL-10 (GUNA) in the modulation of the inflammatory response in endometriotic cell lines. 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) have been used for this study. Cells were treated with SKA-Progesterone and SKA-IL10 at low doses (10 pg/ml and 10 fg/ml respectively). Medroxyprogesterone 17-acetate (MPA) was used at a dose of 10 μM as reference treatment. We analyzed the modulation of HSD17B1 levels by WB analysis after low-dose SKA Progesterone and MPA and the 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. 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. 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.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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