Peroxisome proliferator-activated receptor-gamma ligand inhibition of RANTES production by human endometriotic stromal cells is mediated through an upstream promoter element.

OBJECTIVE: To investigate the effect of peroxisome proliferator activated receptor-gamma (PPAR-gamma) ligands on transcription and secretion of regulated upon activation normal T-cell expressed and secreted (RANTES) in endometriotic stromal cells.
DESIGN: Controlled laboratory study.
SETTING: Academic research laboratory. Women in the follicular phase of the menstrual cycle undergoing laparoscopic resection for endometriosis. [1]. Transient transfection of endometriotic stromal cells with RANTES promoter vectors with and without a mutagenized PPAR-gamma response element (PPRE), then treatment with PPAR-gamma ligands; [2]. co-incubation of cells with PPAR-gamma ligands. MAIN OUTCOME MEASURE(S): RANTES promoter activity and RANTES secretion. In endometriotic stromal cells, addition of PPAR-gamma ligands (rosiglitazone and 15 deoxy-Delta(12,14) prostaglandin J(2)) inhibited RANTES promoter activity by 51% and 50%, respectively. In cells transfected with the same promoter after site-directed mutagenesis of the 5' PPRE, addition of PPAR-gamma ligands failed to inhibit promoter activity. When endometriotic stromal cells were treated with PPAR-gamma ligands, a decrease in RANTES secretion by 51% and 20%, respectively, was observed. CONCLUION(S): The PPAR-gamma ligands inhibit RANTES transcription and protein production in endometriotic stromal cells. Transcriptional repression appears to be mediated through a specific PPRE at -344 to -322 bp upstream from the RNA polymerase start site.