Synergistic effect of regulatory T cells and proinflammatory cytokines in angiogenesis in the endometriotic milieu
Synergistic effect of regulatory T cells and proinflammatory cytokines in angiogenesis in the endometriotic milieu
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调节性 T 细胞和促炎细胞因子在子宫内膜异位环境中血管生成中的协同作用
DOI：
10.1093/humrep/dex067
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发表时间：
2017-06
影响因子：
6.1
通讯作者：
Li Da-Jin
中科院分区：
文献类型：
--
作者：
Wang Xiao-Qiu;Zhou Wen-Jie;Luo Xue-Zhen;Tao Yu;Li Da-Jin
STUDY QUESTION: Do regulatory T cells (Tregs) contribute to angiogenesis in endometriosis?.SUMMARY ANSWER: High levels of CCL17 and CCL22 cause the recruitment of Tregs, upregulate the immunosuppression of Tregs and, in turn, may promote angiogenesis in endometrial cells in synergy with proinflammatory cytokines..WHAT IS ALREADY KNOWN: The peritoneal fluid of patients with endometriosis has a higher percentage of Tregs than that of normal individuals; however, the regulatory role of Tregs in the disease remains unclear..STUDY DESIGN, SIZE, DURATION: This study used primary human endometrial stromal cells (ESCs), monocytes (Mo), Tregs and human umbilical vein endothelial cells (HUVECs). All experiments were performed at least three times..PARTICIPANTS/MATERIALS, SETTING, METHODS: The migration of Tregs was evaluated by the transwell migration assay. The activation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase and p38 signaling pathways was examined using the In- Cell WesternTM (LI-COR®) western blot analysis system, as well as by traditional western blot analysis. Changes in the expression of CCL22, CCL17, transforming growth factor-beta 1 (TGF-β1), Interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), IL-8 and vascular endothelial growth factor (VEGF) in cell-culture supernatant were detected by ELISA. We analyzed the Tregs by multicolor flow cytometry to directly test the expression of CCR4, CD4, CD25, Foxp3, CTLA-4, CD39 and CD73..MAIN RESULTS AND THE ROLE OF CHANCE: Our results showed that ESCs-Mo co-culture produced significantly higher levels of CCL22 and CCL17 than ESCs or Mo cultured alone, and that estradiol (E2) or progesterone (P) further promoted this upregulation, demonstrating stronger chemotaxis on Tregs. The co-culture of ESCs with Mo stimulated TGF-β1 secretion by Tregs, which could be inhibited by anti-CCL22 or/and anti-CCL17 neutralizing antibodies (Abs). The expression of CCR4 by Tregs was upregulated in ESCs-Mo co-culture, especially by treatment with E2 and/or P, and this effect could be abolished by anti-CCL22 and/or anti-CCL17-neutralizing Abs. The Treg-ESCs-Mo coculture treated with E2 (10−8 mol/l) and P (10−8mol/l) could enhance the immunosuppression of Tregs, as proved by the elevated expression of Foxp3, CTLA-4, CD39 and CD73 on Tregs. ESCs-Mo co-culture could significantly promote the secretion of IL-1β and TNF-α. TGF-β1 from Tregs could activate p38/ERK1/2 signaling pathways in ESCs, and IL-1β and TNF-α produced by ESCs-Mo co-culture had synergistic roles with TGF-β1. TGF-β1 and the proinflammatory cytokines IL-1β or TNF-α could synergistically promote IL-8 and VEGF expression in ESCs via the p38/ERK1/2 signaling pathways. The high levels of IL-8 and VEGF in the supernatant of ESCs stimulated the angiogenesis of HUVECs..LARGE SCALE DATA: None..LIMITATIONS, REASONS FOR CAUTION: This study was only performed in vitro using eutopic ESCs, instead of ectopic cells, from.endometriosis patie
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影响因子：
12.4
作者：
Ahern D;Lloyd CM;Robinson DS
通讯作者：
Robinson DS
DOI：
10.1084/jem.194.6.847
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Iellem A;Mariani M;Lang R;Recalde H;Panina-Bordignon P;Sinigaglia F;D'Ambrosio D
通讯作者：
D'Ambrosio D
DOI：
10.1016/s0020-7292(02)00308-9
发表时间：
2002-12-01
影响因子：
3.8
作者：
Barcza, E;Rózewska, ES;Marianowski, L
通讯作者：
Marianowski, L
DOI：
10.1016/j.ejogrb.2004.11.044
发表时间：
2005-09
期刊：
European journal of obstetrics, gynecology, and reproductive biology
影响因子：
--
作者：
J. Skrzypczak;M. Szczepańska;E. Puk;M. Kamieniczna;M. Kurpisz
通讯作者：
J. Skrzypczak;M. Szczepańska;E. Puk;M. Kamieniczna;M. Kurpisz
影响因子：
6.7
作者：
Shi, Ying-Li;Luo, Xue-Zhen;Li, Da-Jin
通讯作者：
Li, Da-Jin