Iron overload-modulated nuclear factor kappa-B activation in human endometrial stromal cells as a mechanism postulated in endometriosis pathogenesis

Alvarado-Díaz, Carlos Patricio; Núñez, Marco Tulio; Devoto, Luigi; González-Ramos, Reinaldo

Keywords: endometrium, iron overload, endometriosis, NF-kB, ICAM-1

Abstract

OBJECTIVE: To evaluate the effect of iron overload on nuclear factor kappa-B (NF-κB) activation in human endometrial stromal cells (ESCs). DESIGN: Experimental study. SETTING: University hospital research laboratory. PATIENT(S): Ten healthy women. INTERVENTION(S): 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. MAIN OUTCOME MEASURE(S): 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. RESULT(S): 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. CONCLUSION(S): 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.

Más información

Título de la Revista: FERTILITY AND STERILITY
Volumen: 103
Número: 2
Editorial: Elsevier Science Inc.
Fecha de publicación: 2015
Página de inicio: 439
Página final: 447
Idioma: English
Financiamiento/Sponsor: FONDECYT 11080123, FONDAP 15010006-8, PIA-CONICYT ACT1114
DOI:

10.1016/j.fertnstert.2014.10.046

Notas: BIOSIS; Chemical Abstracts; Current Contents; MEDLINE; EMBASE; Nutrition Abstracts; Science Citation Index; Scopus