Reinaldo González-Ramos1, Sylvie Defrère, Luigi Devoto. 1. Instituto de Investigaciones Materno Infantil, Departamento de Obstetricia y Ginecología, Hospital Clínico San Borja-Arriarán, Facultad de Medicina, Universidad de Chile, Santiago, Chile. rgonzalezr@med.uchile.cl
Abstract
OBJECTIVE: To update, analyze, and summarize the literature concerning nuclear factor-kappaB (NF-κB) participation in endometriosis pathophysiology. DESIGN: Review. RESULT(S): Nuclear factor-kappaB is physiologically activated in the human endometrium, showing variable activity. A cyclic p65-DNA binding pattern was shown in the endometrium of healthy women. This cyclic pattern was altered in the endometrium of patients with endometriosis. Nuclear factor-kappaB is basally activated in peritoneal endometriotic lesions, showing higher p65 activity in red endometriotic lesions than in black lesions. In vivo and in vitro studies show up-regulation of inflammation and cell proliferation and down-regulation of apoptosis by NF-κB activity. Iron overload has been shown in the pelvic cavity of endometriosis patients, and iron overload and oxidative stress activate NF-κB in macrophages, which have been shown to participate in the endometriosis-associated inflammatory reaction. CONCLUSION(S): Nuclear factor-kappaB activation dysregulation in the endometrium of endometriosis patients may explain some endometrial biological alterations associated with endometriosis. The scientific evidence strongly suggests that NF-κB activity in endometriotic cells stimulates inflammation and cell proliferation and inhibits apoptosis, favoring the development and maintenance of endometriosis. Iron overload in the pelvic cavity of endometriosis patients could be a main factor enhancing oxidative stress and activating NF-κB in a chronic manner, contributing to endometriosis establishment and growth.
OBJECTIVE: To update, analyze, and summarize the literature concerning nuclear factor-kappaB (NF-κB) participation in endometriosis pathophysiology. DESIGN: Review. RESULT(S): Nuclear factor-kappaB is physiologically activated in the human endometrium, showing variable activity. A cyclic p65-DNA binding pattern was shown in the endometrium of healthy women. This cyclic pattern was altered in the endometrium of patients with endometriosis. Nuclear factor-kappaB is basally activated in peritoneal endometriotic lesions, showing higher p65 activity in red endometriotic lesions than in black lesions. In vivo and in vitro studies show up-regulation of inflammation and cell proliferation and down-regulation of apoptosis by NF-κB activity. Iron overload has been shown in the pelvic cavity of endometriosispatients, and iron overload and oxidative stress activate NF-κB in macrophages, which have been shown to participate in the endometriosis-associated inflammatory reaction. CONCLUSION(S): Nuclear factor-kappaB activation dysregulation in the endometrium of endometriosispatients may explain some endometrial biological alterations associated with endometriosis. The scientific evidence strongly suggests that NF-κB activity in endometriotic cells stimulates inflammation and cell proliferation and inhibits apoptosis, favoring the development and maintenance of endometriosis. Iron overload in the pelvic cavity of endometriosispatients could be a main factor enhancing oxidative stress and activating NF-κB in a chronic manner, contributing to endometriosis establishment and growth.
Authors: Britton Trabert; Ligia Pinto; Patricia Hartge; Troy Kemp; Amanda Black; Mark E Sherman; Louise A Brinton; Ruth M Pfeiffer; Meredith S Shiels; Anil K Chaturvedi; Allan Hildesheim; Nicolas Wentzensen Journal: Gynecol Oncol Date: 2014-08-23 Impact factor: 5.482