Estrogen receptor β upregulates CCL2 via NF-κB signaling in endometriotic stromal cells and recruits macrophages to promote the pathogenesis of endometriosis

作者：Yanling Gou, Xue Li, Peiling Li, Hongyan Zhang, Tenghan Xu, Hao Wang, Beidi Wang, Xuesong Ma, Jiang Xue, Zongfeng Zhang · 发表于：Human Reproduction · 年份：2019 · DOI：10.1093/humrep/dez019 · 被引用次数：136 · 研究领域：Endometriosis Research and Treatment、Reproductive System and Pregnancy、Cytokine Signaling Pathways and Interactions

STUDY QUESTION: How is the activation of estrogen receptor β (ERβ) in endometriotic stromal cells (ESCs) involved in macrophage recruitment to promote the pathogenesis of endometriosis? SUMMARY ANSWER: ERβ modulates the production of C-C motif chemokine ligand 2 (CCL2) via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in ESCs and thus recruits macrophages to ectopic lesions to promote pathogenesis. WHAT IS KNOWN ALREADY: Macrophages are mainly recruited to the peritoneal cavity to promote the pathogenesis of endometriosis. Recent studies have demonstrated that ERβ plays an important role in the progression of endometriosis through modulating apoptosis and inflammation. STUDY DESIGN, SIZE, DURATION: An observational study consisting of 22 cases (women with endometriosis, diagnosed by laparoscopy and histological analysis) and 14 controls (without endometriosis) was carried out. PARTICIPANTS/MATERIALS, SETTING, METHODS: Tissues and stromal cells that were isolated from 22 patients with ovarian endometrioma and deeply infiltrating endometriosis were compared with tissues and stromal cells from 14 patients with normal cycling endometrium using immunohistochemistry, quantitative PCR, Western blot, cell migration assay and cloning formation assay. P values < 0.05 were considered significant, and experiments were repeated in at least three different cell preparations. MAIN RESULTS AND THE ROLE OF CHANCE: We observed that accumulated macrophages wer...