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.


METHODS
In vitro experimental study using flow cytometry, ELISA, semiquantitative reverse transcriptase polymerase chain reaction, and Western blot.


METHODS
Postgraduate Institute of Medical Education and Research.


METHODS
Twenty-five women undergoing laparoscopy (n = 10) and laparotomy (n = 15).


METHODS
Endometriotic cyst wall (group I) and endometrial biopsy (group II) collection.


METHODS
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.


RESULTS
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.


CONCLUSIONS
The data of the present study provide new insights for the implication of atorvastatin treatment for endometriosis in humans.
Sharma
Indu
I
Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Dhawan
Veena
V
Mahajan
Nitin
N
Saha
Subhash Chand
SC
Dhaliwal
Lakhbir Kaur
LK
D000293:Adolescent; D000328:Adult; D000069059:Atorvastatin; D001706:Biopsy; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004715:Endometriosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D000067616:S100A12 Protein; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014591:Uterine Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018970:Insulin-Like Growth Factor Binding Protein 1; D008070:Lipopolysaccharides; D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D047495:PPAR gamma; D011758:Pyrroles; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D042461:Vascular Endothelial Growth Factor A; D000069059:Atorvastatin; D051546:Cyclooxygenase 2