title: Iron overload-modulated nuclear factor kappa-B activation in human endometrial stromal cells as a mechanism postulated in endometriosis pathogenesis.
abstract: OBJECTIVE
  To evaluate the effect of iron overload on nuclear factor kappa-B (NF-κB) activation in human endometrial stromal cells (ESCs).
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  University hospital research laboratory.
  
  
  METHODS
  Ten healthy women.
  
  
  METHODS
  Isolated ESCs from endometrial biopsies were incubated with 50 μM FeSO(4) or vehicle. The NF-κB inhibitor [5-(p-fluorophenyl)-2-ureido] thiophene-3-carboxamide (TPCA-1), which inhibits IKKβ, the kinase of IκBα (inhibitory protein of NF-κB), was used to prevent iron overload-stimulated NF-κB changes in ESCs.
  
  
  METHODS
  NF-κB activation was assessed by p65:DNA-binding activity immunodetection assay. IκBα, p65, and intercellular adhesion molecule (ICAM)-1 proteins expression was evaluated by Western blots. ESC soluble ICAM (sICAM)-1 secretion was measured by ELISA using conditioned medium.
  
  
  RESULTS
  Iron overload increased p65:DNA-binding activity and decreased IκBα and p65 cytoplasmic expression in ESCs after 30 minutes of incubation as compared with the basal condition. ESC ICAM-1 expression and sICAM-1 secretion were higher after 24 hours of iron overload treatment than in the absence of treatment. TPCA-1 prevented the iron overload-induced increase of p65:DNA binding and IκBα degradation.
  
  
  CONCLUSIONS
  Iron overload activates IKKβ in ESCs, stimulating the NF-κB pathway and increasing ICAM-1 expression and sICAM-1 secretion. These results suggest that iron overload induces a proendometriotic phenotype on healthy ESCs, which could participate in endometriosis pathogenesis and development.
authors.affiliation: Maternal and Child Research Institute, Department of Obstetrics and Gynecology, Faculty of Medicine, San Borja Arriarán Hospital, University of Chile, Santiago, Chile.
authors.forename: Carlos Patricio
authors.initials: CP
authors.lastname: Alvarado-Díaz
authors.affiliation: Cellular Dynamics and Biotechnology Institute, Faculty of Sciences, University of Chile, Santiago, Chile.
authors.forename: Marco Tulio
authors.initials: MT
authors.lastname: Núñez
authors.affiliation: Maternal and Child Research Institute, Department of Obstetrics and Gynecology, Faculty of Medicine, San Borja Arriarán Hospital, University of Chile, Santiago, Chile.
authors.forename: Luigi
authors.initials: L
authors.lastname: Devoto
authors.affiliation: Maternal and Child Research Institute, Department of Obstetrics and Gynecology, Faculty of Medicine, San Borja Arriarán Hospital, University of Chile, Santiago, Chile. Electronic address: rgonzalezr@med.uchile.cl.
authors.forename: Reinaldo
authors.initials: R
authors.lastname: González-Ramos
mesh_terms: D000328:Adult; D000577:Amides / Q000494:pharmacology; D002478:Cells, Cultured; D004715:Endometriosis / Q000139:chemically induced / Q000378:metabolism*; D004717:Endometrium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005290:Ferric Compounds / Q000633:toxicity; D006801:Humans; D019190:Iron Overload / Q000139:chemically induced / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D000577:Amides; D005290:Ferric Compounds; D016328:NF-kappa B; D013876:Thiophenes; C499326:2-((aminocarbonyl)amino)-5-(4-fluorophenyl)-3-thiophenecarboxamide
keywords: Endometriosis; ICAM-1; NF-κB; endometrium; iron overload