Nuclear factor-kappaB: a main regulator of inflammation and cell survival in endometriosis pathophysiology
NF-kB activation upregulates 18 inflammation and cell proliferation and inhibits apoptosis of 19 endometriotic cells. Iron overload-mediated NF-kB activation is postulated as a mechanism 20 favoring endometriosis development.
Reinaldo González-Ramos, M.D., Ph.D., Sylvie Defrère, Ph.D., Luigi Devoto, M.D.
Volume 98, Issue 3, Pages 520-528, September 2012
To update, analyze, and summarize the literature concerning nuclear factor-kappaB (NF-kB) participation in endometriosis pathophysiology.
NF-kB is physiologically activated in 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 endometriosis patients. NF-kB 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 upregulation of inflammation and cell proliferation and downregulation of apoptosis by NF-kB activity. Iron overload has been shown in the pelvic cavity of endometriosis patients and iron overload and oxidative stress activate NF-kB in macrophages, which have been shown to participate in the endometriosis associated inflammatory reaction.
NF-kB activation dysregulation in the endometrium of endometriosis patients may explain some endometrial biological alterations associated to endometriosis. The scientific evidence strongly suggest that NF-kB 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-kB in a chronic manner, contributing to endometriosis establishment and growth.