title: Peroxisome proliferating activating receptor gamma-independent attenuation of interleukin 6 and interleukin 8 secretion from primary endometrial stromal cells by thiazolidinediones.
abstract: OBJECTIVE
  To assess the effect of thiazolidinediones on the regulation of inflammatory cytokines related to endometriosis in endometrial tissue and determine whether these effects occur via activation of the peroxisome proliferating activating receptor gamma (PPAR)-γ.
  
  
  METHODS
  In vitro study using eutopic endometrial tissue.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Premenopausal women undergoing laparoscopy for infertility or abdominal pain.
  
  
  METHODS
  Isolation of endometrial stromal cells and the culture of these cells in the presence of thiazolidinediones, ciglitazone and pioglitazone, both with and without a pretreatment of the specific, irreversible PPAR-γ antagonist GW9662.
  
  
  METHODS
  Quantitation of interleukin (IL)-6 and IL-8 released into the cell culture medium by ELISA. Real-time polymerase chain reaction to quantitate PPAR-γ gene expression in the primary cell preparations and the expression of IL-6 and IL-8 after thiazolidinedione treatment.
  
  
  RESULTS
  Treatment of stromal cells with thiazolidinediones attenuated IL-6 and IL-8 release in a dose-dependent manner. This effect was not inhibited by GW9662 pretreatment. Ciglitazone induced IL-6 messenger RNA expression, an effect that was suppressed by GW9662 pretreatment.
  
  
  CONCLUSIONS
  Thiazolidinediones decrease the proinflammatory cytokines IL-6 and IL-8 in endometrial stromal cells via a PPAR-γ-independent mechanism. A better understanding of the anti-inflammatory action of this class of drugs may improve their safety and efficacy for endometriosis treatment.
authors.affiliation: Department of Obstetrics and Gynecology, Inselspital, Berne University Hospital, University of Berne, Berne, Switzerland. brett.mckinnon@dkf.unibe.ch
authors.forename: Brett
authors.initials: B
authors.lastname: McKinnon
authors.forename: Nick A
authors.initials: NA
authors.lastname: Bersinger
authors.forename: Michael D
authors.initials: MD
authors.lastname: Mueller
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004717:Endometrium / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000893:Anti-Inflammatory Agents; C508606:CXCL8 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; C039671:ciglitazone; D000077205:Pioglitazone