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

Indu Sharma, Veena Dhawan, Dhawan V, Nitin Mahajan, Saha SC, Subhash Chand Saha, Lakhbir Kaur Dhaliwal, Lakhbir Dhaliwal, Dhaliwal LK
Fertility and sterility · 2009 · vol. 94(5) , pp. 1639–1646.e1 · doi:10.1016/j.fertnstert.2009.10.003 · PMID:19944411 · W2141750554
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This study investigated the effects of atorvastatin on lipopolysaccharide-induced gene expression in endometriotic stromal cells in vitro.

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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-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-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-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.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Gene Expression Regulation Heptanoic Acids Lipopolysaccharides Pyrroles Uterine Diseases Adolescent Adolescent Adult Adult Atorvastatin Atorvastatin Biopsy Biopsy Case-Control Studies Case-Control Studies Cell Differentiation Cell Differentiation Cell Differentiation Cell Proliferation

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