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 μg/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-γ (PPAR-γ), and liver X receptor-α (LXR-α) genes in endometrial-endometriotic stromal cells and on levels of insulin-like growth factor binding protein-1 (IGFBP-1) and 17β-E₂ 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-γ and LXR-α) and levels of IGFBP-1 was observed after atorvastatin treatment in both the groups. However, atorvastatin treatment had no effect on 17β-E₂ 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.

Key Words: Endometriosis, inflammation, ESCs, atorvastatin, in vitro