Role of cytokines in development of endometriosis

我们测量了子宫内膜异位症患者腹膜液（PF）中基质金属蛋白酶-9 （MMP-9）、其抑制剂、金属蛋白酶-1组织抑制剂（TIMP-1）和白细胞介素-10 （IL-10）的水平。虽然MMP-9的浓度低于检测水平，但PF中存在高浓度的TIMP-1和IL-10，其中IL-10水平在子宫内膜异位症患者中明显高于无子宫内膜异位症患者。为了研究IL-6或IL-10对TIMP-1基因表达的影响，我们从子宫或卵巢巧克力囊肿中收集子宫内膜和子宫内膜异位症基质细胞。这些细胞因子的刺激作用已被阐明。我们进行了IL-6、可溶性IL-6受体在子宫内膜和子宫内膜异位症细胞生长中的可能作用的研究。我们研究了IL-6、可溶性IL-6受体或两者联合对子宫内膜和子宫内膜间质细胞增殖的影响。IL-6受体对组织增生期基质细胞的生长无影响。相比之下，添加200或400pg/ml的IL-6可显著抑制细胞增殖。同样，可溶性IL-6受体的加入对分泌期组织中子宫内膜基质细胞的生长有明显的抑制作用，但对增殖期没有明显的抑制作用。另一方面，子宫内膜异位症组织间质细胞对IL-6有抗性，无抑制反应。虽然联合治疗不影响增殖期基质细胞和子宫内膜异位症组织的增殖，但在可溶性IL-6受体1ng/ml存在下，10gn/ml可溶性IL-6可抑制分泌期基质细胞的增殖。IL-6受体和gp130转录本在增殖期和分泌期子宫内膜细胞及子宫内膜异位细胞中表达。IL-6可能在调节子宫内膜细胞的生长中发挥核心作用，作为内分泌作用的中介。子宫内膜异位症细胞在IL-6的抑制调控方面可能表现得与正常细胞不同。少

We have measured peritoneal fluid (PF) levels of matrix metalloproteinase-9 (MMP-9), its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-10 (IL-10) in patients with endometriosis. Although the concentrations of MMP-9 was below the detectable level, high concentrations of TIMP-1 and IL-10 were present in the PF. The levels of IL-10 in PF was significantly higher in patients with endometriosis than in patients without endometriosis. In order to examine the effects of IL-6 or IL-10 on the gene expression of TIMP-1, endometrial and endometriotic stromal cells were collected from the uterus or from ovarian chocolate cysts. The stimulatory effects of these cytokines have been elucidated.We have conducted the study to investigate the possible role of IL-6, soluble IL-6 receptor in the growth of endometrial and endometriotic cells. We examined the effect of IL-6, soluble IL-6 receptor or combination of both factors on the proliferation of endometrial and endometriot … More ic stromal cells. IL-6 receptor had no effect on the growth of stromal cells in tissue from the proliferative phase. In contrast, the addition of 200 or 400pg/ml of IL-6 induced significant inhibition of cell proliferation. Similarly, the addition of soluble IL-6 receptor caused significant suppression in the growth of endometrial stromal cells in tissue from the secretory phase, but not the proliferative phase. On the other hand, stromal cells of endometriotic tissues were resistant to IL-6, showing no inhibitory response. Although the combination treatment did not affect the proliferation of stromal cells of proliferative phase and of endometriotic tissues, 10gn/ml of soluble IL-6 inhibited proliferation of stromal cells of the secretory phase in the presence of 1ng/ml of soluble IL-6 receptor. The expression of transcripts of IL-6 receptor and gp130 was observed in the endometrial cells from the proliferative and secretory phases and in endometriotic cells. IL-6 may play a central role in regulation of the growth of endometrial cells as a mediator of endocrine action. Endometriotic cells may behave differently from the normal counterpart in terms of the inhibitory regulation exerted by IL-6. Less