In vitro effects of atorvastatin on lipopolysaccharide-induced gene expression in endometriotic stromal cells

Objective: To investigate the in vitro effects of atorvastatin on lipopolysaccharide (LPS)-induced gene expression in endometrial-endometriotic stromal cells. Design: In vitro experimental study using flow cytometry, ELISA, semiquantitative reverse transcriptase polymerase chain reaction, and Western blot. Setting: Postgraduate Institute of Medical Education and Research. Patient(s): Twenty-five women undergoing laparoscopy (n = 10) and laparotomy (n = 15). Intervention(s): Endometriotic cyst wall (group I) and endometrial biopsy (group II) collection. Main Outcome Measure(s): The endometrial-endometriotic stromal cells were isolated from ectopic (group I) and eutopic (group II) endometrium by established methods, cultured, and stimulated with LPS (1 mu g/mL), followed by atorvastatin treatment in a time-and dose-dependent manner to investigate the effects of LPS on proliferation (Ki-67) and expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), receptor for advanced glycation end products (RAGE), extracellular newly identified RAGE binding protein (EN-RAGE), peroxisome proliferator activated receptor-gamma (PPAR-gamma), and liver X receptor-alpha (LXR-alpha) genes in endometrial-endometriotic stromal cells and on levels of insulin-like growth factor binding protein-1 (IGFBP-1) and 17 beta-E-2 in endometrial-endometriotic stromal cell culture supernatant. Result(s): Significant inhibition of Ki-67 and LPS-induced expression of inflammatory and angiogenic genes (COX-2, VEGF, RAGE, and EN-RAGE) was observed in atorvastatin-treated endometrial-endometriotic stromal cells. In contrast, a significant dose-and time-dependent increase in expression of anti-inflammatory genes (PPAR-gamma and LXR-alpha) and levels of IGFBP-1 was observed after atorvastatin treatment in both the groups. However, atorvastatin treatment had no effect on 17b-E-2 levels in endometrial/endometriotic stromal cell culture supernatant. Conclusion(s): The data of the present study provide new insights for the implication of atorvastatin treatment for endometriosis in humans. (Fertil Steril (R) 2010;94:1639-46. (C) 2010 by American Society for Reproductive Medicine.)