Grandi, Giovanni; Mueller, Michael; Bersinger, Nick A.; Papadia, Andrea; Nirgianakis, Konstantinos; Cagnacci, Angelo; Mc Kinnon, Brett (2016). Progestin suppressed inflammation and cell viability of tumor necrosis factor-α-stimulated endometriotic stromal cells. American journal of reproductive immunology, 76(4), pp. 292-298. Wiley 10.1111/aji.12552
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PROBLEM
Endometriosis is an estrogen-dependent inflammatory disease. Progestins are a first-line treatment for endometriosis via activation of pituitary progesterone receptors and suppression of systemic estrogen: a less than optimal treatment. Increasing evidence is beginning to show that progestins may also influence local endometriotic cells, which may contribute to their clinical efficacy.
METHOD OF STUDY
Endometrial stromal cells (ESC) isolated from women with endometriosis were cultured with TNF-α to simulate an inflammatory environment. ESC were treated with the progestins, medroxyprogesterone acetate (MPA), norethisterone acetate (NETA), or dienogest (DNG) and cytokine mRNA production, protein secretion, and cell viability measured.
RESULTS
DNG, NETA, and MPA suppressed the secretion of interleukin (IL)-6, IL-8, and monocyte chemotactic protein (MCP)-1 from ESC. DNG and NETA only reduced the TNF-α-stimulated mRNA production. All three progestins suppressed TNF-α-stimulated ESC proliferation.
CONCLUSION
Progestins may influence endometriotic stromal cells altering the inflammatory microenvironment and their clinical efficacy.