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

• Published in: Fertility and sterility Vol. 94; no. 6; pp. 1985 - 1994
• Main Authors: González-Ramos, Reinaldo, M.D., Ph.D, Van Langendonckt, Anne, Ph.D, Defrère, Sylvie, Ph.D, Lousse, Jean-Christophe, M.D, Colette, Sebastien, B.Sc, Devoto, Luigi, M.D, Donnez, Jacques, M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2010; Elsevier
• Subjects: Angiogenesis; Animals; apoptosis; Biological and medical sciences; cell proliferation; endometriosis; Endometriosis - etiology; Endometriosis - genetics; Endometriosis - immunology; Endometriosis - metabolism; endometrium; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; inflammation; Inflammation - complications; Internal Medicine; invasion; iron; macrophages; Medical sciences; Models, Biological; NF-kappa B - metabolism; NF-kappa B - physiology; NF-kappaB; Non tumoral diseases; Obstetrics and Gynecology; Signal Transduction - genetics; Signal Transduction - physiology; Uterine Diseases - etiology; Uterine Diseases - genetics; Uterine Diseases - immunology; Uterine Diseases - metabolism; Angiogenesis; macrophages; cell proliferation; invasion; inflammation; endometriosis; endometrium; apoptosis; iron; NF-kappaB; Cell proliferation; Pathogenesis; Gynecology; Endometriosis; Iron; Inflammation; Obstetrics; Invasion; Female genital diseases; Uterine diseases; Transcription factor NFκB; Endometrium; Apoptosis; Macrophage
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/j.fertnstert.2010.01.013

Objective To evaluate the role of nuclear factor-κB (NF-κB) 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-κB in the pathophysiology of endometriosis. In vitro and in vivo studies show that NF-κB–mediated gene transcription promotes inflammation, invasion, angiogenesis, and cell proliferation and inhibits apoptosis of endometriotic cells. Constitutive activation of NF-κB has been demonstrated in endometriotic lesions and peritoneal macrophages of endometriosis patients. Agents blocking NF-κB are effective inhibitors of endometriosis development and some drugs with known NF-κB inhibitory properties have proved efficient at reducing endometriosis-associated symptoms in women. Iron overload activates NF-κB in macrophages. NF-κB activation in macrophages and ectopic endometrial cells stimulates synthesis of proinflammatory cytokines, generating a positive feedback loop in the NF-κB pathway and promoting endometriotic lesion establishment, maintenance and development. Conclusion(s) NF-κB transcriptional activity modulates key cell processes contributing to the initiation and progression of endometriosis. Because endometriosis is a multifactorial disease, inhibiting NF-κB 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.