NLRC5通过抑制ERβ介导的炎症反应发挥抗内膜异位症的作用

子宫内膜异位症被称为慢性炎症性疾病。子宫内膜异位症的发育受到雌激素受体β（ERβ）的严重影响，而在子宫内膜异位症期间，含含含5（NLRC5的NLRS）家族卡域5（NLRC）5（NLRC5）表现出抗炎特性。但是，ERβ介导的子宫内膜异位症是否与NLRC5介导的抗炎有关。这项研究旨在评估关系。从患有子宫内膜异位症的患者中收集了九个病例的子宫内膜组织和十例异位子宫内膜组织，并分析了十个健康肥沃妇女的子宫内膜样品，并使用免疫组织化学（IHC）对ERβ的表达水平进行了定量。随后，我们通过腹膜注射构建了子宫内膜异位症的小鼠模型。我们检测到ERβ，NLRC5，肿瘤坏死因子-Alpha（TNF-α），白介素（IL）-6和IL-10的表达，并测量了子宫内膜异位症小鼠中异位病变的体积。在体外，人类子宫内膜基质细胞（HESC）分别用ERβ过表达和NLRC5过表达的质粒分别转染。然后，我们使用定量实时PCR（QRT-PCR）和Western印迹分析评估了ERβ和NLRC5的表达。此外，我们通过酶联免疫吸附测定法（ELISA）测量了细胞培养上清液中TNF-α，IL-6和IL-10的浓度。此外，我们使用Transwell和伤口愈合测定法评估了HESC的迁移和侵袭能力。抑制NLRC5表达促进了子宫内膜异位症的小鼠的异位病变的发展，上调了促炎性因子TNF-α和IL-6的表达，并下调了抗炎性因子的表达。 NLRC5在子宫内膜异位中的高表达取决于ERβ的过表达。 ERβ促进了hESC的迁移部分取决于炎症微环境。最后，NLRC5过表达抑制了子宫内膜异位症的ERβ介导的发育和炎症反应。有可能为子宫内膜异位症提供新的治疗靶点。

Endometriosis is well known as a chronic inflammatory disease. The development of endometriosis is heavily influenced by the estrogen receptor β (ERβ), while NOD-like receptors (NLRs) family CARD domain-containing 5 (NLRC5) exhibits anti-inflammatory properties during endometriosis. However, whether NLRC5-mediated anti-inflammation is involved in the ERβ-mediated endometriosis is still uncertain. This study aimed to assess that relation.Nine cases of eutopic endometrial tissue and ten cases of ectopic endometrial tissue were collected from patients with endometriosis, and endometrial samples from ten healthy fertile women were analyzed, and the expression levels of ERβ were quantified using immunohistochemistry (IHC). Subsequently, we constructed mouse model of endometriosis by intraperitoneal injection. We detected the expression of ERβ, NLRC5, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-10 and measured the volume of ectopic lesions in mice with endometriosis. In vitro, human endometrial stromal cells (hESCs) were transfected respectively with ERβ-overexpressing and NLRC5-overexpressing plasmids. We then assessed the expression of ERβ and NLRC5 using quantitative real-time PCR (qRT-PCR) and western blot analysis. Furthermore, we measured the concentrations of TNF-α, IL-6, and IL-10 in the cell culture supernatant through enzyme-linked immunosorbent assay (ELISA). Additionally, we evaluated the migration and invasion ability of hESCs using transwell and wound healing assays.Inhibition of NLRC5 expression promotes the development of ectopic lesions in mice with endometriosis, upregulates the expression of pro-inflammatory factors TNF-α and IL-6, and downregulates the expression of anti-inflammatory factor IL-10. The high expression of NLRC5 in endometriosis depended on the ERβ overexpression. And ERβ promoted the migration of hESCs partially depend on inflammatory microenvironment. Lastly, NLRC5 overexpression inhibited ERβ-mediated development and inflammatory response of endometriosis.Our results suggest that the innate immune molecule NLRC5-mediated anti-inflammation participates in ERβ-mediated endometriosis development, and partly clarifies the pathological mechanism of endometriosis, expanding our knowledge of the specific molecules related to the inflammatory response involved in endometriosis and potentially providing a new therapeutic target for endometriosis.