title: Augmented epithelial multidrug resistance-associated protein 4 expression in peritoneal endometriosis: regulation by lipoxin A(4).
abstract: OBJECTIVE
  To compare the expression of the prostaglandin (PG) E(2) transporter multidrug resistance-associated protein 4 (MRP4) in eutopic and ectopic endometrial tissue from endometriosis patients with that of control subjects and to examine whether MRP4 is regulated by the antiinflammatory lipid lipoxin A(4) (LXA(4)) in endometriotic epithelial cells.
  
  
  METHODS
  Molecular analysis in human samples and a cell line.
  
  
  METHODS
  Two university hospitals and a private clinic.
  
  
  METHODS
  A total of 59 endometriosis patients and 32 age- and body mass index-matched control subjects undergoing laparoscopy or hysterectomy.
  
  
  METHODS
  Normal, eutopic, and ectopic endometrial biopsies as well as peritoneal fluid were obtained during surgery performed during the proliferative phase of the menstrual cycle. 12Z endometriotic epithelial cells were used for in vitro mechanistic studies.
  
  
  METHODS
  Tissue MRP4 mRNA levels were quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and localization was analyzed with the use of immunohistochemistry. Cellular MRP4 mRNA and protein were quantified by qRT-PCR and Western blot, respectively. PGE(2) was measured in peritoneal fluid and cell supernatants using an enzyme immunoassay (EIA).
  
  
  RESULTS
  MRP4 was expressed in eutopic and ectopic endometrium, where it was overexpressed in peritoneal lesions and localized in the cytoplasm of glandular epithelial cells. LXA(4) attenuated MRP4 mRNA and protein levels in endometriotic epithelial cells in a dose-dependent manner, while not affecting the expression of enzymes involved in PGE(2) metabolism. Investigations employing receptor antagonists and small interfering RNA revealed that this occurred through estrogen receptor α. Accordingly, LXA(4) treatment inhibited extracellular PGE(2) release.
  
  
  CONCLUSIONS
  We report for the first time that MRP4 is expressed in human endometrium, elevated in peritoneal endometriosis, and modulated by LXA(4) in endometriotic epithelial cells.
authors.affiliation: Department of Gynecology, Obstetrics, and Medical Genetics, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Gori
authors.forename: Yoima
authors.initials: Y
authors.lastname: Rodriguez
authors.forename: Chiara
authors.initials: C
authors.lastname: Pellegrini
authors.forename: Chahin
authors.initials: C
authors.lastname: Achtari
authors.forename: Daniela
authors.initials: D
authors.lastname: Hornung
authors.forename: Eric
authors.initials: E
authors.lastname: Chardonnens
authors.forename: Dorothea
authors.initials: D
authors.lastname: Wunder
authors.forename: Maryse
authors.initials: M
authors.lastname: Fiche
authors.forename: Geraldine O
authors.initials: GO
authors.lastname: Canny
mesh_terms: D000328:Adult; D001202:Ascitic Fluid / Q000378:metabolism; D001706:Biopsy; D015153:Blotting, Western; D016022:Case-Control Studies; D002460:Cell Line; D015232:Dinoprostone / Q000378:metabolism; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007044:Hysterectomy; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D010535:Laparoscopy; D044045:Lipoxins / Q000378:metabolism*; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D010532:Peritoneal Diseases / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015232:Dinoprostone; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D044045:Lipoxins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; C073492:ABCC4 protein, human; C506487:ESR1 protein, human; C040527:lipoxin A4