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 alpha (TNF alpha)-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 TNF alpha (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)-kappa B was evaluated by electrophoretic mobility shift assay. Result(s): Adding TNF alpha (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 TNF alpha and E-2 was significantly reduced by the addition of P, dienogest, or danazol. Electrophoretic mobility shift assay revealed that incubation with TNF alpha and E-2 induced NF-kappa B activation. Adding P, dienogest, or danazol attenuated NF-kappa B activation. Conclusion(s): The present study demonstrates for the first time that P and progestational compounds attenuate the expression of IL-8 by reducing TNF alpha-induced NF-kappa B activation in endometriotic stromal cells, suggesting a possible molecular mechanism of hormone therapy for controlling the growth of endometriosis. (Fertil Sterile (R) 2005;83:1530-5. (c) 2005 by American Society for Reproductive Medicine.)