Iwabe T, Harada T, Tsudo T, Nagano Y, Yoshida S, Tanikawa M, Terakawa N
Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan.
J Clin Endocrinol Metab. 2000 Feb;85(2):824-9. doi: 10.1210/jcem.85.2.6335.
Endometriosis, a common disease among women of reproductive age, is characterized by the presence of endometrial-like tissue outside the uterus. We and others showed that several cytokine levels, including interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNFalpha), are elevated in the peritoneal fluid of women with endometriosis compared with those in women without endometriosis. We also demonstrated that the addition of IL-8 to the culture medium stimulated the proliferation of cultured endometriotic stromal cells. TNFalpha is a multipotent cytokine that induces IL-8 production in various cell types. Therefore, we hypothesized that TNFalpha may also contribute to the pathogenesis of endometriosis by inducing the production of IL-8. To test this hypothesis, we analyzed the peritoneal fluid concentrations of IL-8 and TNFalpha using enzyme-linked immunosorbent assay (ELISA). We observed a significant correlation between the levels of TNFalpha and IL-8 in the peritoneal fluid of endometriosis patients. We also obtained the endometriotic stromal cells from chocolate cyst linings of the ovary. The expression of the receptors for TNFalpha (TNFR) was examined by RT-PCR. We observed the expression of both TNFR-I and TNFR-II genes in endometriotic stromal cells. The expression of IL-8 gene and protein was analyzed by Northern blot hybridization and enzyme-linked immunosorbent assay, respectively. TNFalpha induced the gene and protein expression of IL-8 in endometriotic stromal cells in a dose-dependent fashion. The addition of TNFalpha promoted the proliferation of the endometriotic stromal cells, and the stimulatory effects of TNFalpha were abolished by adding anti-IL-8 antibody. We demonstrated for the first time that TNFalpha stimulated proliferation of endometriotic stromal cells through induction of IL-8 gene and protein expression. We concluded that the TNFalpha may be one of the essential factors for the pathogenesis of endometriosis.
子宫内膜异位症是育龄女性的常见疾病，其特征是子宫外出现类似子宫内膜的组织。我们和其他研究人员发现，与非子宫内膜异位症女性相比，子宫内膜异位症女性腹腔液中的几种细胞因子水平升高，包括白细胞介素-8（IL-8）和肿瘤坏死因子-α（TNFα）。我们还证明，向培养基中添加IL-8可刺激培养的子宫内膜异位症基质细胞增殖。TNFα是一种多效性细胞因子，可在多种细胞类型中诱导IL-8的产生。因此，我们推测TNFα也可能通过诱导IL-8的产生而参与子宫内膜异位症的发病机制。为了验证这一假设，我们使用酶联免疫吸附测定（ELISA）分析了腹腔液中IL-8和TNFα 的浓度。我们观察到子宫内膜异位症患者腹腔液中TNFα和IL-8水平之间存在显著相关性。我们还从卵巢巧克力囊肿内膜中获取了子宫内膜异位症基质细胞。通过逆转录聚合酶链反应（RT-PCR）检测TNFα受体（TNFR）的表达。我们观察到子宫内膜异位症基质细胞中TNFR-I和TNFR-II基因均有表达。分别通过Northern印迹杂交和酶联免疫吸附测定分析IL-8基因和蛋白的表达。TNFα以剂量依赖的方式诱导子宫内膜异位症基质细胞中IL-8的基因和蛋白表达。添加TNFα可促进子宫内膜异位症基质细胞的增殖，而添加抗IL-8抗体可消除TNFα的刺激作用。我们首次证明TNFα通过诱导IL-8基因和蛋白表达刺激子宫内膜异位症基质细胞增殖。我们得出结论，TNFα可能是子宫内膜异位症发病机制的重要因素之一。
