IL-17A Contributes to the Pathogenesis of Endometriosis by Triggering Proinflammatory Cytokines and Angiogenic Growth Factors.
IL-17A Contributes to the Pathogenesis of Endometriosis by Triggering Proinflammatory Cytokines and Angiogenic Growth Factors.
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DOI：
10.4049/jimmunol.1501138
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发表时间：
2015-09-15
期刊：
影响因子：
--
通讯作者：
Tayade C
中科院分区：
文献类型：
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作者：
Ahn SH;Edwards AK;Singh SS;Young SL;Lessey BA;Tayade C
子宫内膜异位症是一种慢性炎症性疾病，其特征是子宫内膜组织在子宫外的异常位置生长。新血管生成或建立新的血液供应是子宫内膜异位症病变在腹膜腔内存活的基本要求之一。IL-17A是一种强有力的促血管生成和促炎细胞因子，参与了几种慢性炎症性疾病的病理生理过程，如类风湿性关节炎和牛皮癣。然而，在子宫内膜异位症的情况下，可获得的信息很少。在这项研究中，我们论证了IL-17A在子宫内膜异位症的发病机制和病理生理学中的潜在重要性。这些数据显示IL-17A在人类异位内膜病变和配对的子宫内膜异位症患者在位内膜中的表达存在差异。重要的是，手术切除病变导致血浆IL-17A浓度显著降低。免疫组织化学显示IL-17A主要定位于匹配的异位和在位组织标本的间质中。IL-17A刺激子宫内膜癌细胞、Ishikawa细胞和人脐静脉内皮细胞后，血管生成因子(血管内皮生长因子、IL-8)、促炎细胞因子(IL-6、IL-1β)和趋化细胞因子(G-CSF、CXCL12、CXCL1、CX3CL1)显著增加。此外，IL-17A以剂量依赖的方式促进基质支架上培养的人脐静脉内皮细胞的小管生成。因此，我们提供了子宫内膜异位病变产生IL-17A的第一个证据，并且通过腹腔镜手术切除病变导致全身IL-17A水平显著降低。综上所述，我们的数据显示，IL-17A可能在促进血管生成和促进腹膜腔内的促炎环境中发挥重要作用，以建立和维持子宫内膜异位症病变。
Endometriosis is a chronic, inflammatory disease characterized by the growth of endometrial tissue in aberrant locations outside the uterus. Neo-angiogenesis or establishment of new blood supply is one of the fundamental requirements of endometriotic lesion survival in the peritoneal cavity. IL-17A is emerging as a potent angiogenic and pro-inflammatory cytokine involved in the pathophysiology of several chronic inflammatory diseases such as rheumatoid arthritis and psoriasis. However, sparse information is available in the context of endometriosis. In this study, we demonstrate the potential importance of IL-17A in the pathogenesis and pathophysiology of endometriosis. The data show a differential expression of IL-17A in human ectopic endometriotic lesions and matched eutopic endometrium from women with endometriosis. Importantly, surgical removal of lesions resulted in significantly reduced plasma IL-17A concentrations. Immunohistochemistry revealed localization of IL-17A primarily in the stroma of matched ectopic and eutopic tissue samples. In vitro stimulation of endometrial epithelial carcinoma cells, Ishikawa cells and human umbilical vein endothelial cells with IL-17A revealed significant increase in angiogenic (VEGF, IL-8), pro-inflammatory (IL-6, IL-1β) and chemotactic cytokines (G-CSF, CXCL12, CXCL1, CX3CL1). Furthermore, IL-17A promoted tubulogenesis of HUVECs plated on matrigel in a dose-dependent manner. Thus we provide the first evidence that endometriotic lesions produce IL-17A and that the removal of the lesion via laparoscopic surgery leads to the significant reduction in the systemic levels of IL-17A. Taken together, our data shows a likely important role of IL-17A in promoting angiogenesis and pro-inflammatory environment in the peritoneal cavity for the establishment and maintenance of endometriosis lesions.