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

Indu Sharma, Veena Dhawan, Nitin Mahajan, Subhash Chand Saha, Lakhbir Kaur Dhaliwal

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1639-1646.e1
JournalFertility and Sterility
Volume94
Issue number5
DOIs
StatePublished - Oct 2010

Keywords

  • ESCs
  • Endometriosis
  • atorvastatin
  • in vitro
  • inflammation

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