PPAR-gamma decreases endometrial stromal cell transcription and translation of RANTES in vitro.
An important step in the monthly turnover of the endometrial lining during the menstrual cycle is the cyclical recruitment and activation of inflammatory cells. Regulated Upon Activation Normal T Cell Expressed and Secreted (RANTES) has been shown to mediate inflammatory cell chemotaxis. This study investigated the effect of PPAR-gamma ligands upon transcription and translation of RANTES in human endometrial stromal cells. First, the expression of endogenous PPAR-gamma was confirmed in endometrial stromal cells. The human RANTES promoter was searched to identify likely PPAR response elements (PPREs), in which three putative sites were found. The effect of PPAR-gamma ligands upon RANTES promoter activity and protein production was analyzed. In cells transfected with RANTES promoter vectors containing 958 bp and 3 PPREs, the addition of PPAR-gamma ligands inhibited promoter activity by 60% (P < 0.01) and 48% (P < 0.02), respectively. Truncation of the gene promoter to delete all putative PPREs abrogated the ligand-induced inhibition. Stromal cells showed a 40% decrease in RANTES protein secretion when treated with a PPAR-gamma ligand (P < 0.01). The use of PPAR-gamma ligands to reduce chemokine production and inflammation may be a productive strategy for future therapy of endometrial disorders, such as endometriosis.
Pritts
Elizabeth A
EA
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, California 94143, USA.
Zhao
Dong
D
Ricke
Emily
E
Waite
Leslie
L
Taylor
Robert N
RN
D000328:Adult; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors* / Q000235:genetics*; D004717:Endometrium / Q000502:physiology*; D005260:Female; D006801:Humans; D008024:Ligands; D014176:Protein Biosynthesis / Q000187:drug effects*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000077154:Rosiglitazone; D017154:Stromal Cells / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
D018946:Chemokine CCL5; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone