Involvement of the nuclear factor-κB pathway in the pathogenesis of endometriosis

Objective: To evaluate the role of nuclear factor-kappa B (NF-kappa B) in the pathogenesis of endometriosis. Design: A literature search was conducted in PubMed to identify all relevant citations. Result(s): Our findings highlight the important role of NF-kappa B in the pathophysiology of endometriosis. In vitro and in vivo studies show that NF-kappa B-mediated gene transcription promotes inflammation, invasion, angiogenesis, and cell proliferation and inhibits apoptosis of endometriotic cells. Constitutive activation of NF-kappa B has been demonstrated in endometriotic lesions and peritoneal macrophages of endometriosis patients. Agents blocking NF-kappa B are effective inhibitors of endometriosis development and some drugs with known NF-kappa B inhibitory properties have proved efficient at reducing endometriosis-associated symptoms in women. Iron overload activates NF-kappa B in macrophages. NF-kappa B activation in macrophages and ectopic endometrial cells stimulates synthesis of proinflammatory cytokines, generating a positive feedback loop in the NF-kappa B pathway and promoting endometriotic lesion establishment, maintenance and development. Conclusion(s): NF-kappa B transcriptional activity modulates key cell processes contributing to the initiation and progression of endometriosis. Because endometriosis is a multifactorial disease, inhibiting NF-kappa B appears to be a promising strategy for future therapies targeting different cell functions involved in endometriosis development, such as cell adhesion, invasion, angiogenesis, inflammation, proliferation, and apoptosis. Upcoming research will elucidate these hypotheses. (Fertil Steril (R) 2010;94:1985-94. (C) 2010 by American Society for Reproductive Medicine.)