González-Ramos Reinaldo, Donnez Jacques, Defrère Sylvie, Leclercq Isabelle, Squifflet Jean, Lousse Jean-Christophe, Van Langendonckt Anne
Department of Gynecology, Université Catholique de Louvain, Cliniques Universitaires St Luc, Avenue Hippocrate 10, 1200 Brussels, Belgium.
Mol Hum Reprod. 2007 Jul;13(7):503-9. doi: 10.1093/molehr/gam033. Epub 2007 May 5.
Red (active), black and white endometriotic lesions are characteristic of peritoneal endometriosis. The transcription factor nuclear factor-kappa B (NF-kappaB) activates proinflammatory, proliferative and antiapoptotic genes in many cell types. To determine whether NF-kappaB is activated in peritoneal endometriosis in women, and further ascertain the differential inflammatory status of endometriotic implants, NF-kappaB activation and intercellular adhesion molecule (ICAM)-1 expression were investigated in peritoneal endometriotic lesions according to their type. Furthermore, p65 and p50 subunits of active NF-kappaB dimers were evaluated in endometriotic lesions to gain some insight into NF-kappaB-implicated pathways. Thirty-six biopsies of peritoneal endometriotic lesions were analyzed. Constitutive NF-kappaB activation, involving p65- and p50-containing dimers, was demonstrated in peritoneal endometriotic lesions by electrophoretic mobility shift assays and supershift analyses, as well as NF-kappaB (p65) DNA-binding activity immunodetection assays. NF-kappaB activation and ICAM-1 expression (evaluated by immunoblotting) were significantly higher in red lesions than black lesions, whereas IkappaBalpha (NF-kappaB inhibitory protein) expression was constant, as shown by western blot analysis. This is the first study to demonstrate constitutive NF-kappaB activation in peritoneal endometriosis in women. NF-kappaB activation and ICAM-1 expression in red lesions confirm the more extensive inflammatory pattern of these lesions compared with black lesions. The involvement of p50/p65 dimers in NF-kappaB activation suggests implication of the classic NF-kappaB activation pathway, making it an attractive therapeutic target in endometriosis.
红色（活跃型）、黑色和白色子宫内膜异位病变是腹膜子宫内膜异位症的特征。转录因子核因子-κB（NF-κB）可激活多种细胞类型中的促炎、增殖和抗凋亡基因。为了确定NF-κB在女性腹膜子宫内膜异位症中是否被激活，并进一步确定异位内膜植入物的不同炎症状态，根据其类型对腹膜子宫内膜异位病变中的NF-κB激活和细胞间黏附分子（ICAM）-1表达进行了研究。此外，还对异位内膜病变中活性NF-κB二聚体的p65和p50亚基进行了评估，以深入了解与NF-κB相关的信号通路。对36例腹膜子宫内膜异位病变活检标本进行了分析。通过电泳迁移率变动分析和超迁移分析以及NF-κB（p65）DNA结合活性免疫检测试验，在腹膜子宫内膜异位病变中证实了涉及含p65和p50二聚体的组成型NF-κB激活。如蛋白质印迹分析所示，红色病变中NF-κB激活和ICAM-1表达（通过免疫印迹评估）显著高于黑色病变，而IκBα（NF-κB抑制蛋白）表达保持恒定。这是第一项证明女性腹膜子宫内膜异位症中存在组成型NF-κB激活的研究。与黑色病变相比，红色病变中NF-κB激活和ICAM-1表达证实了这些病变具有更广泛的炎症模式。p50/p65二聚体参与NF-κB激活提示经典NF-κB激活途径与之相关，使其成为子宫内膜异位症一个有吸引力的治疗靶点。
