缺氧在子宮內膜異位基質細胞中調控介白素-6和介白素-8的機制之探討

Endometriosis is one of the most common gynecological diseases in women during reproductive age. It is characterized by the persistence and growth of vascularized endometrial tissue at ectopic sites, and is associated with pelvic pain and infertility. Although several hypotheses have been proposed, the etiology of endometriosis is still enigmatic. One of the most important pathological roles of endometriosis is chronic pelvic inflammation. Several inflammatory cytokines including interleukin-1 (IL-1), IL-6, IL-8 and tumor necrosis factor-α, are elevated in peritoneal fluid, which contributes to the formation of endometriosis through influencing the establishment and proliferation of ectopic endometrial implants and further cytokine secretion by macrophages. Endometrial stromal cells suffer from hypoxic stress after retrograding to pelvic capacity. Hypoxia is known to be a common pathophysiological feature that regulates gene expression and affects disease processes. Our previous studies demonstrated that hypoxia inducible factor-1α (HIF-1α) is upregulated in endometriotic stromal cells. Therefore, we hypothesized that overexpression of IL-6 and IL-8 in ectopic stromal cells might be induced by hypoxia. Our results demonstrated that IL-6 and IL-8 were overexpressed in ectopic endometriotic implants than that in eutopic stromal cells. Endometrial stromal cells treated with hypoxia significantly induced the expression of IL-6 and IL-8. We further demonstrated that hypoxia-regulated IL-6 and IL-8 expressions were not only mediated by transcriptional upregulation but also increased IL-6 and IL-8 mRNA stability. In addition, hypoxia-increased IL-8 expression promoted angiogenesis by tube formation assay. Taken together, treating eutopic stromal cells with hypoxia to mimic endometrial stromal cells suffering from hypoxic environment can induce IL-6 and IL-8 expressions. These data indicate the critical role of hypoxia-induced IL-6 and IL-8 expressions in the development of endometriosis that may shed lights on investigating novel molecular mechanisms of the etiology of endometriosis.