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Reinaldo González-Ramos, M. D. , Ph. D. , Anne Van Langendonckt, Ph. D

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Presentation on theme: "Reinaldo González-Ramos, M. D. , Ph. D. , Anne Van Langendonckt, Ph. D"— Presentation transcript:

1 Involvement of the nuclear factor-κB pathway in the pathogenesis of endometriosis 
Reinaldo González-Ramos, M.D., Ph.D., Anne Van Langendonckt, Ph.D., Sylvie Defrère, Ph.D., Jean-Christophe Lousse, M.D., Sebastien Colette, B.Sc., Luigi Devoto, M.D., Jacques Donnez, M.D., Ph.D.  Fertility and Sterility  Volume 94, Issue 6, Pages (November 2010) DOI: /j.fertnstert Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions

2 Figure 1 Nuclear factor-κB (NF-κB) subunits and dimers and IκBα protein. RHD: Rel homology domain, responsible for DNA binding, dimerization, and association with IκB proteins; TAD: transcriptional activation domain; AR: ankyrin repeats, responsible for cytoplasmic retention and inhibition of NF-κB (preventing DNA binding). Peptides p50 and p52 derive from precursor proteins p105 and p100 and lack a TAD. Dimers in the fifth row therefore lack TADs. Dimers in the final row are not able to bind to DNA. Adapted from references (41) and (42). Fertility and Sterility  , DOI: ( /j.fertnstert ) Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions

3 Figure 2 Nuclear factor-κB (NF-κB) activation pathways. UV: ultraviolet radiation; LTβR: lymphotoxin-β receptor; BAFF: B-cell-activating factor of the tumor necrosis factor (TNF) family; LMP1: latent membrane protein-1; Tyr K: tyrosine kinase; CK2: casein kinase-II; P: phosphorylation; UB: ubiquitination; NIK: NF-κB-inducing kinase. Adapted from references (30) and (43). Fertility and Sterility  , DOI: ( /j.fertnstert ) Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions

4 Figure 3 Nuclear factor-κB (NF-κB) activation in endometriosis. Activated macrophages secrete cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α), which activate NF-κB in endometriotic cells (EcCs) and macrophages, amplifying the inflammatory response. Iron overload in the peritoneal cavity and in peritoneal macrophages may impair macrophage phagocytic function and activate NF-κB. Iron could also activate NF-κB in EcCs. NF-κB activation in EcCs enhances synthesis of proinflammatory mediators as well as factors of antiapoptosis, growth, invasion, and angiogenesis. NF-κB transcriptional activity could also be responsible for ICAM-1 and RANTES expression and secretion, attracting more macrophages to sites of inflammation. Fertility and Sterility  , DOI: ( /j.fertnstert ) Copyright © 2010 American Society for Reproductive Medicine Terms and Conditions


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