Lousse Jean-Christophe, Van Langendonckt Anne, Defrere Sylvie, Ramos Reinaldo Gonzalez, Colette Sebastien, Donnez Jacques
Universite Catholique de Louvain, Institut de Recherche Experimentale et Clinique, Department of Gynecology, 1200 Brussels, Belgium.
Front Biosci (Elite Ed). 2012 Jan 1;4(1):23-40. doi: 10.2741/e358.
Peritoneal endometriosis is a chronic inflammatory disease characterized by increased numbers of peritoneal macrophages and their secreted products. Inflammation plays a major role in pain and infertility associated with endometriosis, but is also extensively involved in the molecular processes that lead to peritoneal lesion development. Peritoneal oxidative stress is currently thought to be a major constituent of the endometriosis-associated inflammatory response. Excessive production of reactive oxygen species, secondary to peritoneal influx of pro-oxidants such as heme and iron during retrograde menstruation, may induce cellular damage and increased proinflammatory gene expression through nuclear factor-kappa B activation. In particular, prostaglandin biosynthetic enzyme expression is regulated by this transcriptional factor, and increased peritoneal prostaglandin concentrations have been demonstrated in endometriosis. In the light of available data collected from patient biopsies, as well as in vitro and in vivo studies, the respective involvement and potential molecular interactions of iron, nuclear factor-kappa B and prostaglandins in the pathogenesis of endometriosis are explored and discussed. The key role of peritoneal macrophages is emphasized and potential therapeutic targets are examined.
腹膜子宫内膜异位症是一种慢性炎症性疾病，其特征是腹膜巨噬细胞数量及其分泌产物增多。炎症在与子宫内膜异位症相关的疼痛和不孕中起主要作用，但也广泛参与导致腹膜病变发展的分子过程。目前认为腹膜氧化应激是与子宫内膜异位症相关的炎症反应的主要组成部分。逆行月经期间，诸如血红素和铁等促氧化剂进入腹膜，导致活性氧的过量产生，这可能通过核因子-κB激活诱导细胞损伤并增加促炎基因表达。特别是，前列腺素生物合成酶的表达受该转录因子调节，并且在子宫内膜异位症中已证实腹膜前列腺素浓度升高。根据从患者活检以及体外和体内研究收集的现有数据，探讨并讨论了铁、核因子-κB和前列腺素在子宫内膜异位症发病机制中的各自作用及潜在的分子相互作用。强调了腹膜巨噬细胞的关键作用，并研究了潜在的治疗靶点。
