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

Iron overload activates the nuclear factor kappa-B pathway, increasing the expression of intercellular adhesion molecule-1 (ICAM-1) and the secretion of soluble ICAM-1 by endometrial stromal cells, suggesting a new mechanism that may be involved in the pathogenesis of endometriosis.

Carlos Patricio Alvarado-Díaz, Ph.D., Marco Tulio Núñez, Ph.D., Luigi Devoto, M.D., Reinaldo González-Ramos, M.D., Ph.D.

Volume 103, Issue 2, Pages 439-447


To evaluate the effect of iron overload on nuclear factor kappa-B (NF-κB) activation in human endometrial stromal cells (ESCs).

Experimental study.

University hospital research laboratory.

Ten healthy women.

Isolated ESCs from endometrial biopsies were incubated with 50 μM FeSO4 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.

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.

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.

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