Selam Belgin, Kayisli Umit A, Akbas G Eda, Basar Murat, Arici Aydin
Yale University School of Medicine, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, New Haven, Connecticut 06520-8063, USA.
Biol Reprod. 2006 Aug;75(2):203-9. doi: 10.1095/biolreprod.105.045716. Epub 2006 May 10.
Human endometrium is a dynamic tissue under the influence of numerous hormones, growth factors, and cytokines interacting to maintain a balance of cellular growth, differentiation, and apoptosis. We have previously demonstrated that several factors including interleukin-8, extracellular matrix, and steroid hormones modulate FASLG, one of the apoptotic molecules, in human endometrium. Chemokine ligand 2 (CCL2), a monocyte chemoattractant and activating factor, is a cytokine involved in endometrial function. CCL2 is elevated in the peritoneal fluid of women with endometriosis. We hypothesize that increased levels of CCL2 in the endometriotic environment may upregulate FASLG expression in human endometrial stromal cells and induce a local immunotolerance in endometriosis. To test our hypothesis, we studied the in vitro regulation of FASLG expression and apoptosis by CCL2 in endometrial stromal cells. Western blot analysis revealed that CCL2 upregulated FASLG protein expression in cultured endometrial stromal cells. Based on semiquantitative RT-PCR analysis, CCL2 did not alter either FAS or FASLG mRNA expression in endometrial stromal cells. Immunocytochemistry results from the same cells treated with CCL2 demonstrated upregulation of FASLG protein expression. CCL2 did not change rate of apoptosis in endometrial stromal cells as evaluated by TUNEL assay. However, an increased apoptotic rate was detected in Jurkat (T lymphocytes) cells cocultured with endometrial stromal cells previously treated with CCL2. We speculate that increased FASLG expression by CCL2 may induce apoptosis of T lymphocytes and thus produce an immunotolerant environment for the development of ectopic implants.
人子宫内膜是一种动态组织，受多种激素、生长因子和细胞因子相互作用的影响，以维持细胞生长、分化和凋亡的平衡。我们之前已经证明，包括白细胞介素 - 8、细胞外基质和类固醇激素在内的多种因素可调节人子宫内膜中凋亡分子之一的FASLG。趋化因子配体2（CCL2）是一种单核细胞趋化剂和激活因子，是参与子宫内膜功能的一种细胞因子。CCL2在子宫内膜异位症女性的腹腔液中升高。我们假设，在子宫内膜异位症环境中CCL2水平升高可能会上调人子宫内膜基质细胞中FASLG的表达，并在子宫内膜异位症中诱导局部免疫耐受。为了验证我们的假设，我们研究了CCL2对子宫内膜基质细胞中FASLG表达和凋亡的体外调节作用。蛋白质免疫印迹分析显示，CCL2上调了培养的子宫内膜基质细胞中FASLG蛋白的表达。基于半定量逆转录 - 聚合酶链反应分析，CCL2未改变子宫内膜基质细胞中FAS或FASLG的mRNA表达。用CCL2处理的相同细胞的免疫细胞化学结果表明FASLG蛋白表达上调。通过TUNEL检测评估，CCL2未改变子宫内膜基质细胞的凋亡率。然而，在用CCL2预处理的子宫内膜基质细胞共培养的Jurkat（T淋巴细胞）细胞中检测到凋亡率增加。我们推测，CCL2增加FASLG表达可能会诱导T淋巴细胞凋亡，从而为异位植入物的发展产生免疫耐受环境。
