title: Progesterone and progestational compounds attenuate tumor necrosis factor alpha-induced interleukin-8 production via nuclear factor kappa B inactivation in endometriotic stromal cells.
abstract: OBJECTIVE
  To investigate whether and how P, dienogest (synthetic progestin), and danazol affected tumor necrosis factor alpha (TNFalpha)-induced interleukin-8 (IL-8) expression in endometriotic stromal cells.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  Department of Obstetrics and Gynecology, Tottori University Hospital, Yonago, Japan.
  
  
  METHODS
  Ten patients who underwent laparoscopic surgery.
  
  
  METHODS
  Endometriotic stromal cells were obtained from chocolate cyst linings of the ovary.
  
  
  METHODS
  In the presence of TNFalpha (0.1 ng/mL) and E2 (10(-7) mol/L), the cells were cultured in medium with P (10(-6) mol/L), danazol (10(-6) mol/L), or dienogest (10(-7) mol/L). The expression of the IL-8 gene and protein was determined by Northern blotting and ELISA, respectively. Activation of nuclear factor (NF)-kappaB was evaluated by electrophoretic mobility shift assay.
  
  
  RESULTS
  Adding TNFalpha (0.1 ng/mL) together with E2 markedly enhanced gene and protein expression of IL-8. The up-regulation of the IL-8 gene and protein expression by TNFalpha and E2 was significantly reduced by the addition of P, dienogest, or danazol. Electrophoretic mobility shift assay revealed that incubation with TNFalpha and E2 induced NF-kappaB activation. Adding P, dienogest, or danazol attenuated NF-kappaB activation.
  
  
  CONCLUSIONS
  The present study demonstrates for the first time that P and progestational compounds attenuate the expression of IL-8 by reducing TNFalpha-induced NF-kappaB activation in endometriotic stromal cells, suggesting a possible molecular mechanism of hormone therapy for controlling the growth of endometriosis.
authors.affiliation: Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan. tasuku@grape.med.tottori-u.ac.jp
authors.forename: Sayako
authors.initials: S
authors.lastname: Horie
authors.forename: Tasuku
authors.initials: T
authors.lastname: Harada
authors.forename: Masahiro
authors.initials: M
authors.lastname: Mitsunari
authors.forename: Fuminori
authors.initials: F
authors.lastname: Taniguchi
authors.forename: Tomio
authors.initials: T
authors.lastname: Iwabe
authors.forename: Naoki
authors.initials: N
authors.lastname: Terakawa
mesh_terms: D004717:Endometrium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D011372:Progestins / Q000494:pharmacology*; D011446:Prospective Studies; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D011372:Progestins; D014409:Tumor Necrosis Factor-alpha; D011374:Progesterone