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Nuclear factor–kappaB: a main regulator of inflammation and cell survival in endometriosis pathophysiology  Reinaldo González-Ramos, M.D., Ph.D., Sylvie.

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Presentation on theme: "Nuclear factor–kappaB: a main regulator of inflammation and cell survival in endometriosis pathophysiology  Reinaldo González-Ramos, M.D., Ph.D., Sylvie."— Presentation transcript:

1 Nuclear factor–kappaB: a main regulator of inflammation and cell survival in endometriosis pathophysiology  Reinaldo González-Ramos, M.D., Ph.D., Sylvie Defrère, Ph.D., Luigi Devoto, M.D.  Fertility and Sterility  Volume 98, Issue 3, Pages (September 2012) DOI: /j.fertnstert Copyright © 2012 American Society for Reproductive Medicine Terms and Conditions

2 Figure 1 Nuclear factor–kappaB (NF-κB) activation pathways. This is a simplified illustration showing the canonical and atypical NF-κB activation pathways (alternative pathway is not considered, because it has not been studied in the context of endometriosis). P = phosphorylation; U = ubiquitination. Fertility and Sterility  , DOI: ( /j.fertnstert ) Copyright © 2012 American Society for Reproductive Medicine Terms and Conditions

3 Figure 2 Origin of iron overload in the pelvic cavity of endometriosis patients. Erythrocytes are carried into the pelvic cavity by retrograde menstruation and hemorrhaging foci of ectopic endometrium. A proportion of them are phagocytosed by peritoneal macrophages. Metabolism of heme by heme oxygenase (HO) releases iron. Macrophages store some iron in the form of ferritin or hemosiderin and release some that binds to transferrin (Tf). Macrophages are also able to release ferritin into the peritoneal fluid, whereas lysis of erythrocytes releases hemoglobin (Hb) into the peritoneal fluid. Increased pelvic iron concentrations result from Tf, ferritin, and Hb accumulation in the peritoneal fluid. Tf and Hb may be assimilated by ectopic endometrial cells, resulting in the formation of iron deposits (ferritin or hemosiderin) inside lesions. Fertility and Sterility  , DOI: ( /j.fertnstert ) Copyright © 2012 American Society for Reproductive Medicine Terms and Conditions

4 Figure 3 Iron-mediated NF-κB activation theory. Fe = iron; ROS = reactive oxygen species; p65/p50 = NF-κB dimer; IκB = NF-κB inhibitory protein; IKK = IκB kinase complex; TNF = tumor necrosis factor; IL = interleukin; ICAM = intercellular adhesion molecule; MCP = monocyte chemoattractant protein; RANTES = regulated on activation, normal T cell expressed and secreted; GM-CSF = granulocyte macrophage–colony-stimulating factor; COX = cyclooxygenase; VEGF = vascular endothelial growth factor; MIF = macrophage migration inhibitory factor; MMP = matrix metalloproteinase; Bcl = B-cell lymphoma/leukemia; XIAP = X-linked inhibitor of apoptosis protein. Fertility and Sterility  , DOI: ( /j.fertnstert ) Copyright © 2012 American Society for Reproductive Medicine Terms and Conditions


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