Progesterone and progestational compounds attenuate tumor necrosis factor alpha–induced interleukin-8 production via nuclear factor kappaB inactivation in endometriotic stromal cells

Objective To investigate whether and how P, dienogest (synthetic progestin), and danazol affected tumor necrosis factor α (TNFα)-induced interleukin-8 (IL-8) expression in endometriotic stromal cells. Design Prospective study. Setting Department of Obstetrics and Gynecology, Tottori University Hospital, Yonago, Japan. Patient(s) Ten patients who underwent laparoscopic surgery. Intervention(s) Endometriotic stromal cells were obtained from chocolate cyst linings of the ovary. Main Outcome Measure(s) In the presence of TNFα (0.1 ng/mL) and E 2 (10 −7 mol/L), the cells were cultured in medium with P (10 −6 mol/L), danazol (10 −6 mol/L), or dienogest (10 −7 mol/L). The expression of the IL-8 gene and protein was determined by Northern blotting and ELISA, respectively. Activation of nuclear factor (NF)-κB was evaluated by electrophoretic mobility shift assay. Result(s) Adding TNFα (0.1 ng/mL) together with E 2 markedly enhanced gene and protein expression of IL-8. The up-regulation of the IL-8 gene and protein expression by TNFα and E 2 was significantly reduced by the addition of P, dienogest, or danazol. Electrophoretic mobility shift assay revealed that incubation with TNFα and E 2 induced NF-κB activation. Adding P, dienogest, or danazol attenuated NF-κB activation. Conclusion(s) The present study demonstrates for the first time that P and progestational compounds attenuate the expression of IL-8 by reducing TNFα-induced NF-κB activation in endometriotic stromal cells, suggesting a possible molecular mechanism of hormone therapy for controlling the growth of endometriosis.